Brain on Fire:
Anti-NMDA Receptors Encephalitis
ASMA AIT SAID
The Central Nervous System(CNS) is the ultimate priority of the immune system when the human
body is being invaded by any given pathogen.The blood-brain barrier is an actual shield preventing
any potentially harmful microorganism from attending the CNS ensuring thus the safety of neurones
and their functions.However, many types of microorganisms, namely viruses (Herpes simplex virus for
instance) are able to cross this strong wall and reach the human brain resulting in an inflammation
of the brain parenchyma associated with neurological dysfunction causing viral, bacterial or even
fungi encephalitis. Nonetheless, Encephalitis can also be induced by an auto-immune disorder and
the most common one is called anti-NMDA Receptors encephalitis which has been recently discovered.
This illness can be very dangerous and life threatening. Hence, early diagnosis and treatment are
fundamental. In view of the possibility of misdiagnosing it as a primary psychiatric disorder -namely
schizophrenia- this article aims to highlight the principal mechanisms of this auto-immune disease,
the different phases through which patients go, the key to a firm diagnosis and the proper treatment.
Introduction:
T
he etiology of encephalitis is primarily sus-
pected to be viral. However, viral-linked inves-
tigations frequently failed to identify a specific
pathogen. This has led health professionals to make
further research to discover other likely causes among
which auto-immune disorders were detected.
Anti-NMDA receptors encephalitis is an autoimmune
disorder in which the immune system produces
anti-bodies against specific receptors called NMDA
(N-Methyl-D-Aspartate); generating an inflammatory
process in the brain parenchyma. These receptors are
highly expressed in the limbic system (hippocampus,
amygdala, hypothalamus, cingulate gyrus and limbic
cortex) as well as other parts of the CNS. They play
a critical role in synaptic transmission and plasticity
contributing to the control of thoughts, attitude,
emotions and movements. The antibodies addressed
against them engender continued deterioration of
these functions.
This disease can arise in children as well as young
adults. Both male and female with a higher female
prevalence.
Symptoms include prominent psychiatric signs along
with a highly characteristic set of neurological deficits,
cognitive and behavioural manifestations.
Since the emergence of anti-NMDA-R encephalitis in
2007, neurologists and other specialists recognize it
to be a considerable differential diagnosis for viral
encephalitis, on the one hand (especially herpetic
encephalitis) and for psychotic conditions in their early
phase on the other hand; especially schizophrenia
which is marked by similar symptoms to those of the
early stage of anti-NMDAR encephalitis.
What are NMDA receptors? (4,5,10)
NMDAR, along with AMPA and Kainate
receptors, are a sub-type of ionotropic Glutamate
receptors, a category of ligand-gated channels that
bind the major excitatory transmitter in the brain and
spinal cord, in order to open: Amino acid L-Glutamate.
NMDA receptors are made of two sub-units: NR1 and
NR2. Each binding a specific substance: the former
binds to Glutamate and the latter to Glycine. NR1 was
proved to be the main target of the produced anti-
bodies (4).
These receptors are typically clustered at post-
synaptic sites in the membrane, taking a great part
of excitatory synapses of the mature nervous system.
NMDA receptors have many interesting features. They
are permeable to Ca2+ ions,as well as to Na+ and
K+ ions. Their opening depends on both membrane
voltage as well as the nature of the neuro-transmitter.
The binding of glutamate to the NR2 subunit depends
on the concentration of the glycine in extra cellular
space which is quite effective under normal conditions.
The ionic current is controlled by extra cellular Mg2+.
In fact, at resting membrane potentials, Mg2+ binds
to a specific site of the ligand-binding channels,
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