postures. Brainstem reflexes are usually normal, but the
visual threat reflex is absent, as well as spontaneous
eyes movements.
Hyperkinetic phase and neurologic complications:
Oro-facial dyskenias progressively develop after the
akinetic phase. The patient is caught licking or biting his/
her lip, chewing, clenching his/her teeth or grimacing.
Jaw opening dystonia, intermittent ocular movements
and athetoid dystonic postures of the fingers are also
noticed. Because the speed, the distribution and the
motor pattern of these dyskenesias fluctuate from a
moment to another, they can unlawfully lead us to think
of a psychogenic movement disorder. Seizures however
reinforce the diagnosis of anti-NMDAR encephalitis as
they are present in 80% of cases. They are especially
prominent at this stage but could be very intense and
frequent at the onset of the illness; regardless of their
unpredictable occurrence.
In thepediatric population, abnormal movements
appear early on in the progression ofdisease; unlike in
adults where they come into sight at the last phase.
Other important features to emphasize at this phase,
are signs of instability of the autonomic nervous system;
including -among others- : hyperthermia, diaphoresis,
tachycardia or bradycardia and erratic blood pressure.
The patients can also experience severe central
hypoventilation giving rise to a potential coma.
Anti-NMDA receptors encephalitis and tumor:
A few years before this illness was attested
to be an auto-immune disorder, similar symptoms
(psychiatric symptoms, memory deficits, occurrence of
seizures, decreased consciousness, sever oral facial
dyskinesia, autonomic instability and hypoventilation)
were identified in young women (4) who had an
associatedtumor which was particularly benign
(astoundingly found to be an ovarian Teratoma). Later,
biological experiences made on lab rats identified not
only the presence of neural tissue in the tumor; but also,
the NMDA Receptors (2) (3). Hence, many hypotheses
suggested the possibility of the antibodies being
initially formed to attack these receptors within the
tumor itself and secondarily invaded the CNS to bind to
the existing NMDAR. The mechanism was consequently
thought to be exclusively a paraneoplastic disorder.
However, today this condition is shown to appear
independently of a tumor.
The presence of the tumor is related to age, gender
and race. Women past eighteen years of age (and
somewhat predominantly black women) were found to
be more frequently subjected to the tumor in question.
Tumor screening is hence imperative in every patient
diagnosed with Anti-NMDA receptors encephalitis.
Especially that the removal of the tumor along with the
immunotherapy proved a better response to treatment
and less neurological recurrences and relapses.
These patients should benefit from a regular
examination even after tumor resection, given the
possibility of its re-emergence.
Diagnosis of the disease:
After clinically suspecting anti-NMDAR
encephalitis, it is critical to expose the antibodies
addressed against these receptors in the serum and
principally in the Cerebral Spinal Fluid (CSF) of which
the analysis usually reveals pleocytosis and elevated
levels of proteins. The finding of oligoclonal bands
(which are usually present in 60% of cases) (7,8)
indicating the inflammation of the CNS, in multiples
samples makes a firm diagnosis of this illness.
Other imaging techniques are also essential but not
always contributing to the diagnosis. As a matter of fact,
50% of the cases present a normal brain MRI. When
it is abnormal, MRI shows T2 or FLAIR hypersignals
in cortical or subcortical brain regions (7,8,9). EEG is
commonly abnormal and exhibits slow and chaotic
activity in the delta/theta range, sometimes overlapped
with electrographic seizures (8).
Brain biopsy does not provide a firm diagnosis. Studies
have shown normal or non-specific findings such as
microglial activation.
Since the anti-NMDAR encephalitis can be
paraneoplastic especially in young women, a tumor,
precisely the ovarian teratoma, needs to be spotted if
present by MRI, CT scan or ultrasound.
Treatment and outcomes:
Although it’s a newly discovered syndrome,
experts have come up with clear guidelines for the
treatment of anti-NMDA encephalitis, which is still being
under research. It mainly focuses on immunotherapy and
convenient medical or surgical treatment of the tumor
-if it exists- making the treatment act faster and more
effectively. Corticosteroids and immunoglobulins are
justified in order to handle the immune response. It is
recommended to give them intravenously especially in
agitated patients as well as those presenting autonomic
instability. Plasma exchange can also be effective,
but not in the previous cases. In patients without
an associated tumor, second line immunotherapy is
required (rituximab or cyclophosphamide) (13).
The treatment of this illness usually takes a long
period for patients to fully recover and gain their
normal functions back. This could go on for months
and even years. Which requires continuous supervision
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