Limbic encephalitis

Although the symptoms of the condition may vary from person to person, the presenting sign of limbic encephalitis is severe impairment of short-term memory, with most patients having difficulties in recall. Epileptic seizures are common and may occur prior to symptoms of memory loss.^[2] A variety of symptoms may be associated with limbic encephalitis such as anterograde amnesia (the inability to store new memories after the onset of the condition), anxiety, depression, irritability, personality change, acute confusional state, hallucinations and seizures.

Other possible symptoms may include obsessiveness, hyperthermia (increase in body temperature), weight change, sleep disturbances, endocrine dysfunction, aphasia, and apraxia.^[4][2] The symptoms associated with limbic encephalitis can develop over a few days, weeks, or months. It is important to note the neurological symptoms generally precede diagnosis of the malignancy in 60%-75% of patients that have paraneoplastic limbic encephalitis.^[1]

Limbic encephalitis is thought to be caused by a reaction of the immune system to various stimuli such as cancers, tumors, infections, and generalized autoimmune disorders.^[3] In many patients, limbic encephalitis is associated with a tumor or cancer. This is known as paraneoplastic limbic encephalitis (PLE). PLE is most commonly associated with small cell lung cancer (SCLC), which is present in 40% of cases. It may additionally be associated with breast cancer, testicular cancer, and nearly any other tumor.^[4][2] Limbic encephalitis can also occur in the absence of cancer, known as non-paraneoplastic limbic encephalitis (NPLE), such as in the case of a viral infection (for example herpes simplex virus) or systemic autoimmune disorders. In some instances, the cause of limbic encephalitis may never be determined.^[2][3]

Diagnosis of limbic encephalitis can be made when all three of the following criteria have been met:[14588]

1. Subacute onset (rapid progression of less than 3 months) of working memory deficits (short-term memory loss), altered mental status, or psychiatric symptoms

2. At least one of the following:

   • New focal CNS findings
   • Seizures not explained by a previously known seizure disorder
   • CSF pleocytosis (white blood cell count of more than five cells per mm3)
   • MRI features suggestive of encephalitis

3. Reasonable exclusion of alternative causes

Examples of conditions that must be ruled out before a diagnosis of limbic encephalitis can be made, include:^[5]

• Infection (herpes simplex virus, cytomegalovirus, adenovirus, HIV)
• Acute disseminating encephalomyelitis (ADEM) 
• Degenerative diseases (Creutzfeldt-Jakob disease, rapidly progressing Alzheimer disease)
• Nutritional deficiencies (thiamine deficiency)
• Recreational drugs/alcohol
• Metabolic disturbances
• Connective tissue disorders (systemic lupus erythematosus)
• Primary or secondary tumor of the central nervous system

A team of leading autoimmune encephalitis researchers have established diagnostic criteria for limbic encephalitis. View the full position paper, entitled A Clinical Approach to Diagnosis of Autoimmune Encephalitis.

For more on diagnosis, visit the following link to the International Autoimmune Encephalitis Society Web site:
https://autoimmune-encephalitis.org/diagnosis

Treatment for limbic encephalitis varies depending on the underlying cause. In cases of confirmed paraneoplastic limbic encephalitis (PLE), removal or treatment of the tumor is often the first step in treatment. If the cause of limbic encephalitis is a viral infection, an antiviral drug may be prescribed. Immunotherapy is often utilized as a first line or second line treatment.^[6][2] If immunotherapy fails, medications such as rituximab or cyclophosphamide may be considered.^[2]

The prognosis for limbic encephalitis varies from person to person and is based on the underlying cause of the condition. For example, individuals that have small cell lung carcinoma (SCLC) and test positive for an antibody called anti-Hu, tend to respond poorly to treatment, whereas individuals that have an ovarian teratoma and test positive for the NMDAR antibody respond well to treatment.^[1]

Given evidence that paraneoplastic limbic encephalitis may occur prior to identification of a tumor, if a tumor is not initially identified, regular tumor screening may be recommended to occur after treatment is completed.^[2]