Limbic Encephalitis and Autoimmune Responses

Limbic encephalitis is a neurological condition where the limbic system is inflamed, leading to various symptoms, including memory loss, confusion, and mood changes. It is often triggered by an immune response.

Previously, the main trigger for limbic encephalitis was thought to be underlying cancer. However, recent research suggests that the trigger is often unknown. This means that the immune system may attack the limbic system without a clear cause.

LGI1 antibodies are a type of protein found in the blood that are associated with limbic encephalitis. They are found in over 70% of limbic encephalitis cases, even those without cancer.

J.A.N. Corsellis was a neuropathologist who made significant contributions to the understanding of limbic encephalitis. He coined the term, linked the symptoms to brain pathology, and highlighted the association with underlying cancer.

The limbic lobe, a region of the brain involved in emotions, memory, and behavior, is a key area affected in limbic encephalitis. It includes the amygdala, hippocampus, and cingulate gyrus.

Early clinical descriptions of limbic encephalitis often involved patients experiencing memory loss, confusion, and personality changes. These symptoms often progressed gradually, leading to significant deterioration.

The neuropathological findings in limbic encephalitis are characterized by neuronal loss, gliosis (scarring in the brain), and inflammatory infiltrates. These changes primarily occur in the limbic lobe.

The limbic lobe is the primary region affected in limbic encephalitis. This region is involved in various critical functions, including emotions, memory, and behavior. Damage to this area can lead to the characteristic symptoms of limbic encephalitis.

Antibodies directed against an antigen expressed by neurons and tumor cells. These antibodies were linked to limbic encephalitis, an autoimmune response triggered by tumors.

A type of limbic encephalitis that does not associate with cancer and often responds well to immunotherapy. The antibodies target voltage-gated potassium channels.

A protein associated with voltage-gated potassium channels (VGKCs). It is the actual target of antibodies in VGKC-associated limbic encephalitis.

A set of neurological disorders characterized by inflammation of the limbic system, the part of the brain responsible for emotions and memory. This inflammation leads to seizures, memory problems, and behavioral changes.

A type of limbic encephalitis that is associated with cancer, particularly small-cell lung cancer (SCLC).

A type of limbic encephalitis that is not linked to cancer. Its cause is unknown.

A type of receptor that binds to the neurotransmitter glutamate.

A type of receptor that binds to the neurotransmitter GABA.

Besides infection by herpesvirus, HIV seroconversion, Whipple's disease, and neurosyphilis, these are other infectious disorders that may mimic limbic encephalitis.

Patients with neurosyphilis often experience seizures. It can be tricky to tell neurosyphilis apart from limbic encephalitis.

Some cases of limbic encephalitis occur with systemic autoimmune diseases like lupus, Sjögren's, or Behçet's disease. However, you need to investigate for autoimmune encephalitis before attributing the symptoms to the underlying systemic disease.

Hashimoto encephalopathy is a condition where the immune system attacks the thyroid gland. This can also lead to limbic encephalitis. Antibodies against the amino terminal domain of α-enolase are sometimes associated with this type of encephalitis.

Although α-enolase antibodies have been reported in cases of Hashimoto encephalopathy, they've also been found in other conditions like Creutzfeldt–Jakob disease and limbic encephalitis with LGI1 antibodies. This highlights the need to carefully test for multiple antibodies before diagnosing Hashimoto encephalopathy as the cause of limbic encephalitis.

The table provides a breakdown of different disorders that might be mistaken for autoimmune limbic encephalitis. By examining features of these conditions such as whether they cause inflammation in the medial temporal lobes, CSF pleocytosis, distinctive features, and laboratory tests used for diagnosis, we can rule out other potential causes.

This table showcases the complexity of diagnosing limbic encephalitis. It highlights the importance of considering a wide range of disorders that might share similar symptoms. Ruling out these other possibilities can help in accurately diagnosing the appropriate cause for the patient's condition.

A viral infection, usually with a focus on the medial temporal lobes of the brain, that can cause encephalitis. It is often associated with memory loss, confusion, and behavioral changes.

The presence of Herpes Simplex Virus DNA in the Cerebrospinal Fluid (CSF). This is a strong indicator of Herpes Simplex Encephalitis.

Inflammation of the brain tissue.

A type of brain tumor that can be associated with limbic encephalitis.

Increased numbers of white blood cells in the Cerebrospinal Fluid (CSF).

A test used to diagnose encephalitis. It involves examining the brain tissue for signs of inflammation and other abnormalities.

A type of imaging test that uses magnetic fields to create detailed images of the brain.

Anti-GABAbR limbic encephalitis is a severe form of autoimmune encephalitis specifically associated with small-cell lung cancer (SCLC). It has a poorer prognosis compared to other forms of autoimmune encephalitis.

KCTD16 antibodies are found in a significant majority of patients with anti-GABAbR limbic encephalitis associated with SCLC. This suggests a strong link between KCTD16 antibodies and this specific type of encephalitis.

AMPAR antibodies are associated with a form of autoimmune encephalitis that primarily affects the limbic system. This type of encephalitis often presents with features of limbic involvement in around 60% of patients.

Patients with AMPAR antibody-associated encephalitis frequently present with confusion, cognitive deficits like memory loss, and changes in behavior. Seizures are less common compared to other types of encephalitis.

The presence of psychiatric manifestations or concurrent onconeural antibodies, including anti-CV2 (CRMP5), are associated with a poorer response to treatment in AMPAR antibody-associated encephalitis.

Ophelia syndrome is a specific type of autoimmune encephalitis associated with Hodgkin lymphoma. It can present with typical limbic encephalitis features or more extensive, widespread symptoms.

In patients with anti-GABAbR encephalitis without detectable tumor, the presence of KCTD16 antibodies might suggest the presence of an underlying, undetected small-cell lung cancer.

Aggressive immunotherapy, in addition to treating the underlying tumor, is recommended for patients with anti-GABAbR limbic encephalitis associated with SCLC due to its poor prognosis.

Neuronal antibodies are proteins that target brain cells. These antibodies can help predict how a patient will respond to treatment and how likely they are to fully recover.

Antibodies against intracellular antigens are linked to severe, irreversible neuronal damage, resulting in a poor prognosis for treatment. These occur when the immune system mistakenly targets the inside of nerve cells.

Antibodies against neuronal cell membrane antigens usually indicate reversible neuronal dysfunction. This means the damage to nerve cells is potentially reparable, leading to a better chance of recovery with treatment.

Paraneoplastic limbic encephalitis is a condition where the limbic system is inflamed and triggered by cancer. Hu (ANNA1) and Ma2 antibodies are frequently associated with this specific type of encephalitis.

Paraneoplastic encephalomyelitis involves inflammation in multiple areas of the nervous system, including the brain, spinal cord, and nerves. This condition is often associated with the Hu (ANNA1) antibodies.

Hu (ANNA1) antibodies are often associated with paraneoplastic encephalomyelitis, a condition where multiple areas of the nervous system are inflamed. Initial symptoms may resemble limbic encephalitis but often progress to involve more widespread areas of the nervous system.

Paraneoplastic encephalomyelitis is a serious neurological condition characterized by widespread inflammation throughout the nervous system, often linked to certain cancers. The clinical symptoms vary depending on the specific areas of the nervous system affected by the inflammation.