NMDA-receptor antibody encephalitis
This paper was written by Dr Sarosh Irani and Professor Angela Vincent from the Department
of Clinical Neurology, University of Oxford.
The major role of our immune system is to recognize and clear infection. Sometimes,
however the components of the immune system – antibodies and white blood cells -
may react with our own body to cause autoimmune diseases. When this reaction is
against the brain, an autoimmune encephalitis is produced. Many cases of autoimmune
encephalitis have recently been reported with antibodies against the N-methyl D-aspartate
receptor (NMDAR). NMDARs help modulate the excitability of nerves and therefore
antibodies against these receptors are likely to have an important role in directly
causing the disease.
The clinical features of NMDAR-antibody associated encephalitis are distinctive
and are prompting many clinicians to request the NMDAR-antibody test to diagnose
this condition. The disease predominantly affects young patients, with around 30%
of cases under 18 years of age. Females are affected more commonly than males
Once a patient has been diagnosed with NMDAR-antibody encephalitis, an underlying
tumour should be excluded. While very few males have tumours detected (typically
<10%), recent reports suggest that between 20 and 57% of females may have an underlying
tumour (Dalmau et al 2008, Irani et al 2010). This tumour is most commonly an ovarian
teratoma and is itself a benign tumour but is thought to stimulate the antibody
production.
At onset, the most distinctive features include prominent psychiatric symptoms with
seizures, confusion and memory loss. Patients will sometimes show bizarre and often
rather disturbing behaviours. Typically 10 to 20 days later, patients often develop
a movement disorder, fluctuations in blood pressure, heart rate and temperature
and may have a reduction in their level of consciousness. The movement disorder
often consists of continuous writhing and twitching of face and limbs but can also
be a generalised slowing-down of movements.
If this clinical pattern is recognized, other causes excluded (particularly infections)
and the antibody result is positive, treatments should be started. Treatments consist
of immune therapies (such as steroids, immunoglobulins and plasma exchange) and
removal of a tumour, if present. Prompt therapies offer a good chance of substantial
recovery in the majority of patients. However, such recovery is usually slow and
many patients who return to work only do so after a year or two.
In summary, NMDAR-antibody encephalitis is a newly-described antibody-mediated disease
that causes psychiatric features, confusion, memory loss and seizures followed by
a movement disorder, loss of consciousness and autonomic fluctuations. The disease
can respond well albeit often slowly to various immunotherapies and removal of an
underlying tumour.
References: Dalmau et al 2008 Irani et al 2010
Last modified: May 2012