Anti-Hu associated encephalitis, also known as Anti-ANNA1 associated encephalitis, is an uncommon form of brain inflammation that is associated with an underlying cancer. It can cause psychiatric symptoms such as depression, anxiety, and hallucinations. It can also produce neurological symptoms such as confusion, memory loss, weakness, sensory loss, pain, seizures, and problems coordinating the movement of the body.
While its cause is unknown, the most common hypothesis is that it is caused by an immune system attack on the nervous system. This immune system attack is linked to cancer in most cases, usually small cell lung carcinoma. The condition's namesake, the anti-Hu antibody, is a protein made by the host's immune system, and it is present in virtually all cases. Treatment is focused on removing the underlying cancer and suppressing the immune system. Its prognosis remains quite poor, with most patients dying less than a year after diagnosis.
Signs and symptoms
The signs and symptoms can vary in onset, quality, duration, severity, and response to treatment. Symptoms tend to present acutely over days to weeks. Its symptoms depend on which areas of the brain the disease affects, because specific parts of the brain have particular functions.
Many cases involve an attack on the limbic system, which includes structures like the amygdala, hippocampus, and thalamus. Respectively these brain regions regulate anger, fear, memory formation, and motor and sensory signaling. Affected persons may develop memory loss and may have sudden changes in personality. This is often accompanied by headaches, delusions, or hallucinations.
In some cases, the antibodies created by this illness attack another structure of the brain called the brainstem. The brainstem is responsible for basic bodily functions like breathing, but not more complex actions and emotions, which is why the presentation is different when the disease affects the limbic system than when it affects the brainstem. Symptoms may include dizziness, nausea, vomiting, and decreased breathing which may progress to respiratory failure.
Cause
Anti-Hu associated encephalitis is a syndrome associated with cancer. However, occasionally it occurs without cancer being present. Proteins react within the brain and change behavior and basic biological functions. Primarily adults contract this illness, and typically they have an underlying cancer that is either undiagnosed, diagnosed, in remission, or cured.
The condition can occur at any point during cancer. Small cell lung cancer is a particularly aggressive cancer more common in smokers and is associated with anti-Hu encephalitis. Neuroblastoma is a cancer more frequently affecting children, and despite the relatively low rates of anti-Hu among children with neuroblastoma, these are the most likely children to have anti-Hu associated encephalitis.
Pathophysiology
Nearly all people with the condition have anti-Hu antibodies in their serum. The antibody is produced by the body as an immune system response to Hu proteins, which are naturally clustered within the nuclei of neurons in the central and peripheral nervous system. The condition can involve a number of neural structures including the brainstem, cerebellum, spinal cord, dorsal roots, peripheral nerves, and the limbic system of the brain.
There is a debate about whether the antibody is a cause of, rather than an effect of, the disease process. Older studies suggested the antibodies caused the disease, pointing to the discovery of antibody deposition in the brain tissue of patients at autopsy. However, the injection of the antibodies into mice did not produce any disease, and the deposition of antibody was often not at the places where brain damage was greatest. Newer studies suggest the antibodies are an effect, not a cause, of the condition, with a consensus that a patient's own T cells are playing a major role in the disease process. These T cells may be activated by the Hu proteins.