Earlier this week we presented a case of a young healthy woman presenting with acute onset delirium, autonomic instability and CSF pleocytosis.
Here’s how you all answered.
Looks like this was a pretty difficult question! The correct answer is…
Anti-N-methyl-D-aspartate receptor antibodies
That was a tough one! Most of you were thrown off by the freshwater swimming and picked Naegleriasis. Lets examine the answer choices:
A. Naegleria fowleri: This species of amoeba lives in bodies of fresh water (including under-treated swimming pools!) and is responsible for the extremely rare but deadly disease Primary Amoebic Meningoencephalitis (also Naegleriasis). Classic symptoms include fever, seizures, confusion and ataxia and the pathogen has a case fatality rate of 95%!. While our patient does show some of these signs and symptoms, Naegleriasis would not explain her autonomic instability.
B. West Nile Virus: While possible, WNV neuroinvasive disease is less likely in this patient with autonomic instability, normal reflexes and a lymphocytic pleocytosis
C. Rabies: While her symptoms are quite classic for rabies, our patient has no known risk factors for rabies exposure.
D. CNS Sarcoidosis: The chronicity of symptoms and lack of neuroimaging findings argue against neurosarcoid.
E. Bartonella hensellae: Cat scratch disease rarely causes an agitated delirium
Correct Answer: Anti-N-methyl-D-aspartate Receptor Antibodies
Anti-NMDA-R encephalitis was first described in 2007 and is thought to be an autoimmune encephalitis caused by antibodies against the NR-1 and NR-2 subtypes of the NMDA receptor. This receptor binds glutamate and glycine and is predominantly localized to the hippocampus, forebrain, basal ganglia and cerebellum, regions of the brain responsible for memory, personality, movement and autonomic regulation. Over 100 confirmed cases of this form of autoimmune meningoencephalitis have been reported since 2007. Interestingly, one single-center retrospective study identified anti-NMDA-R antibodies in the CSF of 87% (6/7) patients with compatible clinical features and a diagnosis of encephalitis NOS.
Most patients who develop anti-NMDA-R encephalitis are young women and the classic presentation is a viral prodrome followed by acute agitation, seizures, autonomic instability, and personality changes. The largest case series to date showed a strong female predominance (91% of cases). Interestingly, a strong association exists betwen anti-NMDA-R meningoencephalitis and ovarian teratoma. Pathologic studies of these tumors have shown neural tissue expressing NMDA-R suggesting an autoimmune mechanism.
New York Post writer Susan Callahan wrote an autobiography of her experience with anti-NMDA-R meningoencephalitis titled Brain on Fire: My month of Madness. Read more about anti-NMDA-R meningoencephalitis here and here.
Stay Tuned for the next Case Challenge!
Sources: Day, High et.al JGIM 2011; Pruss, Dalmau et.al. Neurology 2010; A Barista With Autonomic Neuropathy and Delirium. Medscape. May 07, 2012; https://en.wikipedia.org/w/index.php?title=Anti-NMDA_receptor_encephalitis&oldid=665323664