Because some RPDs can be reversed with early treatment, Geschwind has been advocating for an efficient differential diagnostic algorithm based on the acronym VITAMIN, which is short for Vascular, Inflammatory (infectious and noninfectious), Trauma/Toxins, Autoimmune, Metabolic, Idiopathic, and Neoplastic.

“Many [RPDs] are treatable if diagnosed early enough, which is why I got into this field,” said Geschwind. “The ones that aren’t treatable are neurodegenerative, and if the toxic metabolic ones are diagnosed too late, those also might not be treatable.”

Steven Vernino, MD, professor of neurology and neurotherapeutics at the University of Texas Southwestern Medical Center in Dallas, specializes in autoimmune encephalopathies. As a referral center, he said they see a fair number of treatable autoimmune RPDs each year. These include anti-N-methyl D-aspartate (anti-NMDA) receptor antibody encephalitis, paraneoplastic limbic encephalitis (PLE), and autoimmune limbic encephalitis associated with potassium channel-related antibodies, such as leucine-rich, glioma-inactivated 1 (LGI-1) antibody.


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Vernino said anti-NMDA disorder was only recognized in the last 10 years, so the incidence is unknown. According to the Encephalitis Society, it is associated with prominent psychiatric symptoms at onset including anxiety, mania, social withdrawal, and psychosis.4  It has been seen in young children, women, and older adults, presenting as either encephalopathy and dementia or seizures.

PLE is a rapidly progressing dementia in cancer patients caused by autoimmune attack on the brain. Most individuals with PLE will turn out to have a rarely seen cancer of the lung, thymus gland, breast, or testes.

Voltage-gated potassium channel-complex antibody-associated limbic encephalitis (VGKC-LE) affects men at roughly twice the rate of women. Initially, family members notice that their relative becomes forgetful, drowsy, and withdrawn. Patients can also develop mood disorders (like depression) or bizarre thoughts and behaviors.5

“If a patient presents with what we think might be an autoimmune encephalopathy because of the tempo and other features,” Vernino said, “then we typically order a panel of antibodies that would include paraneoplastic antibodies, anti-NMDA antibodies, and potassium channel-related antibodies. If all [those] come back negative, it is hard to be sure about the diagnosis.”

Those are the most challenging to diagnose, he said, because they are all potentially treatable, especially the anti-NMDA receptor encephalitis and the potassium channel antibody-related encephalitis.

“Patients can do quite well, but sometimes you have to be pretty aggressive in terms of the immune treatments, which is challenging without a diagnostic test that confirms the diagnosis,” Vernino said. “This is an evolving field, however, and there is a lot of excitement in the autoimmune world about finding better diagnostic tests and perhaps [identifying more treatable] patients than we know about now, which is always a good thing.”

Michael O’Leary is a freelance medical writer based in the greater Seattle Area. This article was medically reviewed by Pat F. Bass III, MD, MS, MPH

References

  1. Encyclopedia of Mental Disorders. http://www.minddisorders.com/Del-Fi/Dementia.html
  2. Geschwind MD, Haman A, Miller BL. Rapidly progressive dementia. Neurol Clin. 2007;25(3):783-807.
  3. Kovacs GG, Peden A, Weis S et al. Rapidly progressive dementia with thalamic degeneration and peculiar cortical prion protein immunoreactivity, but absence of proteinase K resistant PrP: a new disease entity?Acta Neuropathol Commun. 2013;1(1):72.
  4. Irani SR, Vincent A. The Encephalitis Society. “NMDA Receptor Associated Encephalitis.” April 2010/ February 2014. Available at: http://www.encephalitis.info/information/types-of-encephalitis/types-of-autoimmune-encephalitis/nmda-receptor-associated-encephalitis/
  5. Miller T. The Encephalitis Society. “Voltage-gated Potassium Channel-complex Antibody-associated Limbic Encephalitis’ (VGKC-LE).” May 2014. Available at: http://www.encephalitis.info/information/types-of-encephalitis/types-of-autoimmune-encephalitis/voltage-gated-potassium-channel-complex-antibody-associated-limbic-encephalitis/

All electronic documents accessed Nov. 10, 2014.