Autoimmune brain disorders are also called autoimmune encephalitis. This happens when the body’s immune system mistakenly attacks the brain or spinal cord, leading to an inflammatory response. Autoimmune encephalitis is not common and is sometimes misdiagnosed or undiagnosed.
What is autoimmune encephalitis?
The word encephalitis refers to inflammation of the brain, which can be caused by an infection or an autoimmune reaction. In autoimmune encephalitis, the inflammation is caused by the attack of neuronal cell surface and synaptic antigens by antibodies produced by the immune system. Autoimmune encephalitis is also often associated with cancers, this is called paraneoplastic encephalitis.
Memory loss is a common symptom of autoimmune encephalitis.
What are the signs and symptoms of autoimmune encephalitis?
Autoimmune encephalitis has diverse causes and aetiologies, symptoms can have many variations and often overlap with symptoms of other neurological conditions. Common symptoms observed in autoimmune encephalitis include:
Neurological symptoms
Seizures
Abnormal movements
Speech problems
Vision problems
Weakness
Loss of sensation and numbness,
Trouble walking and keeping balance
Muscle weakness and stiffness
Bladder and bowel issues
Psychiatric symptoms
Psychosis
Auditory and visual hallucinations
Paranoia
Behavior changes such as agitation and compulsiveness
Anxiety or panic attacks
Sleep disorders
Cognitive symptoms
Memory loss
Confusion
Cognitive impairment
Altered mental status
Physical symptoms
Fever
Weight loss
Many of these symptoms are also observed in many other neurological conditions, hence a proper medical diagnosis by a neurologist is crucial in detecting autoimmune encephalitis. If you notice yourself or a loved one experiencing these symptoms, please consult your doctor promptly.
What are the types of causes autoimmune encephalitis and their causes?
Autoimmune encephalitis is still under study by scientists as the exact mechanisms of the disease are not clearly defined. Often, they are caused by antibodies produced by the body that attack proteins in the brain which are responsible for communication between nerve cells. In other instances, autoimmune encephalitis can be caused by underlying conditions, such as cancer or infections.
It is believed that an overreaction of the immune system towards self-antigens of the nervous system is what essentially causes the disorder. Doctors and scientists have identified several types of autoimmune encephalitis, such as:
Anti-NMDA receptor encephalitis – Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is the most common type of autoimmune encephalitis. The antibodies target the NMDA receptors, which leads to the gradual depletion of NMDA receptors on the synapses. This leads to symptoms such as seizures, movement disorders and cognitive impairment [1].
Anti-LGI1 encephalitis – Anti-leucin-rich glioma-inactivated 1 (LGI1) encephalitis is a type of limbic encephalitis which typically affects those of age 50 and older. Limbic encephalitis affects the limbic system and hypothalamus.
Anti-CASPR2 encephalitis – Anti-contactin-associated protein-like 2 encephalitis is also a limbic encephalitis, usually associated with Morvan syndrome, a neurological disorder described as hyperactivity of the nervous system. Peripheral nerve excitability is a common symptom of anti-CASPR2 encephalitis, which may appear as muscle twitching, numbness, or tingling sensations.
Anti-GABAA receptor encephalitis – Gamma aminobutyric acid (GABA) are inhibitory neurotransmitters that prevent overactivity or overexcitation of the neurons. Anti-GABAA encephalitis targets GABAA receptors, which consequently result in symptoms such as seizures and status epilepticus [1, 2].
Anti-GABAB receptor encephalitis – Anti-GABAB receptor encephalitis has similar causes and symptoms as Anti-GABAA receptor encephalitis.
Anti-DPPX encephalitis – Dipeptidyl-peptidase-like protein 6 (DPPX) is a subunit of the voltage-gated potassium ion channels found in the gastrointestinal tract and nervous system. Antibodies that target DPPX cause hyperexcitability of these ion channels. Common symptoms include diarrhoea, weight loss, memory loss, delirium, and seizures [1, 3].
Anti-GAD65 encephalitis – Glutamic acid decarboxylase is an enzyme that converts glutamate to GABA, the inhibitory neurotransmitter. Anti-GAD antibodies are also involved in other neurological disorders such as seizures, cerebellar ataxia, stiff-person syndrome, and epilepsy [4].
Anti-AMPA receptor encephalitis – Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are a type of glutamate receptors involved in excitatory neurotransmission in the brain. Anti-AMPA receptor encephalitis has similar symptoms to anti-NMDA receptor encephalitis, and is highly associated with cancer [1, 5].
Anti-IgLON5 disease – Immunoglobulin-like cell adhesion molecule 5 (IgLON5) is a cell adhesion molecule of the IgLON family. Anti-IgLON5 disease is unique as it presents both autoimmune and neurodegenerative symptoms [6]. Common symptoms of anti-IgLON5 disease are sleep disorders, movement disorders, gait instability, bulbar syndrome, and cognitive impairment [6].
Anti-neurexin encephalitis – Neurexin-3 alpha is a cell adhesion molecule involved in synaptic development of the brain. Anti-neurexin-3 alpha encephalitis is relatively new, common symptoms include fever, weight loss, gastrointestinal symptoms, mental confusion, seizures, and decreased levels of consciousness [7]. However, other symptoms have also been reported such as numbness or weakness of the limbs, stinging pain in the eyes, hallucinations and disturbed sleep [8].
Anti-GlyR encephalitis – Glycine is an inhibitory neurotransmitter, glycine receptors (GlyR) are typically found in the spinal cord and brainstem. Anti-GlyR encephalitis typically show symptoms of muscle spasms, stiffness, and progressive encephalitis with rigidity and myoclonus (PERM) [1].
Anti-mGluR1 encephalitis – Metabotropic glutamate receptors (mGluR) are located in the synapses of Purkinje cells of the central and peripheral nervous system, and play a role in brain development, pain perception, memory, and learning. Anti-mGluR1 encephalitis is rare and is associated with lymphoma [1, 10]
Anti-mGluR5 encephalitis – Although similar to mGluR1, mGluR5 is involved in weakening synaptic transmission in the hippocampus. Symptoms of anti-mGluR5 encephalitis are also different from those of anti-mGluR1 encephalitis [1, 11].
Anti-Hu (ANNA-1) encephalitis – Anti-Hu encephalitis is highly associated with small cell lung cancer (more than 80% of patients). Anti-Hu antibodies are also typically used to identify patients with paraneoplastic encephalitis [1].
Anti-Ma2 encephalitis – This type of autoimmune encephalitis is usually found in germ cell tumours in young men. Common symptoms are memory and cognitive impairment, and neuropathy [1].
Who is at risk of autoimmune encephalitis?
Autoimmune encephalitis has many pathological variations, hence the risk factors also vary among the different subtypes. Patient demographics show several similarities among disease subtypes:
Age – Age varies according to the type of autoimmune encephalitis. For example, elderly people of age 60 and above are more at risk of anti-LGI1 and anti-CASPR2 encephalitis, while anti-NMDA receptor encephalitis is more common in children and young adults.
Sex – Similar to age, sex as a risk factor varies according to the type of autoimmune encephalitis. Women are more at risk of anti-NMDA receptor encephalitis. Men may be more at risk of anti-LGI1 encephalitis.
Malignancy – Cancer is often associated with incidences of autoimmune encephalitis [1]. Cancers can express the target antigens that trigger paraneoplastic encephalitis.
Genetics – Autoimmune encephalitis can be caused by genetics, such as anti-IgLON5 disease [9].
Infections – Encephalitis of herpes simplex virus was reported to trigger anti-NMDA receptor encephalitis [10]. In this case, the inflammatory response is separate from the one caused by a herpes simplex encephalitis (HSE), as it was reported to appear 3 months after HSE.
Diagnosis of How is autoimmune encephalitis diagnosed?
Cases of autoimmune encephalitis are rare, signs and symptoms are also non-specific and diverse, hence diagnosis of autoimmune encephalitis can be complicated. A neurologist will have to perform several tests to diagnose autoimmune encephalitis properly [1, 12, 13]:
Clinical examination – The neurologist will assess the patient’s symptoms, medical history, family history, as well as physical and cognitive function.
Imaging tests – An imaging test such as magnetic resonance imaging (MRI) is typically used to observe brain structures and rule out other possible causes for symptoms, such as infections or brain abnormalities [1]. Specific features such as increase in T2 signal in the temporal lobes, may indicate limbic encephalitis [1, 14].
Blood and urine tests – Blood and urine tests are used to check for nutrient deficiencies, medications, hormone levels, or infections [12].
Lumbar puncture – In a lumbar puncture procedure, the cerebrospinal fluid (CSF) is taken then checked for white blood cell count, presence of infectious pathogens, as well as CSF pressure [12, 13].
Antibody tests – Antibody tests are what determines the type of autoimmune encephalitis, blood and CSF samples are used in these tests.
Cancer screening – In cases of paraneoplastic encephalitis, where tumours trigger the onset of the autoimmune disorder, cancer screening is done to detect any malignancies.
Lumbar puncture will aid in the diagnosis of autoimmune encephalitis by obtaining CSF samples for antibody tests.
Treatment of How is autoimmune encephalitis treated?
Available treatments for autoimmune encephalitis [15]:
Corticosteroids – Corticosteroids such as prednisolone, methylprednisolone, and dexamethasone are used to treat the inflammation of autoimmune encephalitis. Corticosteroids are frequently prescribed as first-line medication to treat autoimmune encephalitis.
Intravenous immunoglobulin (IVIG) – IVIG involves collecting plasma from donors, the collected plasma contains antibodies that can neutralise autoantibodies in autoimmune encephalitis. IVIG is usually used in conjunction with steroids, PLEX, rituximab, or other immunotherapy treatments [16].
Plasmapheresis (PLEX) and immunoadsorption – PLEX involves removing the plasma from the patient’s collected blood, a substitute plasma is added and the blood inserted back into the patient’s body. This method essentially removes the autoantibodies that cause the symptoms of autoimmune encephalitis. Immunoadsorption is similar to PLEX, but with selective removal of immunoglobulins from the plasma [16].
Immunosuppressants – Immunosuppressants such as methotrexate, azathioprine, mycophenolate mofetil, and cyclophosphamide are used only when first-line treatments are insufficient. Immunosuppressants essentially reduce the effects of the immune system.
Monoclonal antibodies – The monoclonal antibody rituximab is widely used to treat autoimmune disorders. Rituximab targets B-cell antigen CD20, this causes a reduction in B-cell population and reduces relapses. Monoclonal antibodies are also a second-line therapy for autoimmune encephalitis and are only used when first-line treatments are not effective [16].
IVIG is a first-line immunotherapy treatment for autoimmune encephalitis.
Autoimmune encephalitis is an elusive disease. It is not a common disease, diagnosis and detection are also challenging. However, with the right approach it can be manageable and treatable. Consult our neurologists now if you have any doubts or concerns regarding autoimmune diseases of the brain.
Frequently Asked Questions
Can autoimmune encephalitis be cured?
Autoimmune encephalitis can be treated and patients can recover fully.
Does having autoimmune encephalitis mean I have cancer?
Autoimmune encephalitis is often associated with cancer, but not all patients with autoimmune encephalitis have cancer.
Does autoimmune encephalitis go away on its own?
Unlike viral encephalitis, which can resolve on its own, autoimmune encephalitis is caused by your own body, hence it is very unlikely that it will go away without treatment.
Is autoimmune encephalitis the same as multiple sclerosis (MS)?
Although both autoimmune encephalitis and MS are autoimmune disorders, they are not the same. MS involves immune attacks to the myelin sheath of nerve fibres. Autoimmune encephalitis involves immune attacks on the cell surface, synaptic, and intracellular proteins of the nervous system.
What happens if autoimmune encephalitis is not diagnosed?
Misdiagnosis can delay treatment for autoimmune encephalitis, which may lead to complications such as cognitive impairment, sleep disorders, memory loss, and seizures. Autoimmune encephalitis is often treatment-responsive and patients typically recover completely, especially with early diagnosis.
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