Lewy Body Pathology and Chronic Traumatic Encephalopathy Associated With Contact Sports

Dr. Ann McKee's group last week published an article in the Journal of Neuropathology and Experimental Neurology supporting the theory that contact sports increases the risk of developing neocortical Lewy body disease, which may in part explain the extrapyramidal motor symptoms sometimes observed in patients with chronic traumatic encephalopathy. Dr. Thor Stein is the senior author on the paper, entitled Lewy Body Pathology and Chronic Traumatic Encephalopathy Asssociated with Contact Sports. 

Best Post of November 2014: Robin Williams had Lewy Body Diesease

The next in our "Best of the month" series is from November 18, 2014:

Robin Williams

The official cause of Robin Williams' death, released Friday by the Marin County coroner, was ruled

Williams had long battled alcoholism, drug addiction and depression, but in November 2013 he was diagnosed with Parkinson's disease, according to his widow, after noticing a tremor in his left arm and difficulty moving on his left side as early as 2011.

Now a redacted pathology report from the autopsy on Williams' body has been made public and mentions "Diffuse Lewy body dementia,". Given that Dementia with Lewy Bodies can involve vivid visual hallucinations, it has now been speculated that perhaps such hallucinations may have lead to Williams' death.

Media reports, quoting anonymous "family sources," state that Williams' family believes that Lewy body disease was a critical "triggering" factor in his suicide. If so, this would be an unusual manifestation of the disease. Suicides have not been linked specifically to the hallucinations of Lewy Body Disease in the past.

Dennis Dickson, MD

"The use of the term dementia in the neuropathology report should not be inferred to mean that dementia was observed during life," warns Dennis Dickson of the Mayo Clinic in Jacksonville, who says he reviewed the neuropathology report.

"Mr. Williams was given a clinical diagnosis of (Parkinson's) and treated for motor symptoms. The report confirms he experienced depression, anxiety and paranoia, which may occur in either Parkinson's disease or dementia with Lewy bodies," Dickson said.

Robin Williams had Lewy Body Disease

Robin Williams

The official cause of Robin Williams' death, released Friday by the Marin County coroner, was ruled a suicide by hanging, with no evidence of alcohol or illegal drugs in his system and only therapeutic concentrations of prescribed medications.

Williams had long battled alcoholism, drug addiction and depression, but in November 2013 he was diagnosed with Parkinson's disease, according to his widow, after noticing a tremor in his left arm and difficulty moving on his left side as early as 2011.

Now a redacted pathology report from the autopsy on Williams' body has been made public and mentions "Diffuse Lewy body dementia,". Given that Dementia with Lewy Bodies can involve vivid visual hallucinations, it has now been speculated that perhaps such hallucinations may have lead to Williams' death.

Media reports, quoting anonymous "family sources," state that Williams' family believes that Lewy body disease was a critical "triggering" factor in his suicide. If so, this would be an unusual manifestation of the disease. Suicides have not been linked specifically to the hallucinations of Lewy Body Disease in the past.

Dennis Dickson, MD

"The use of the term dementia in the neuropathology report should not be inferred to mean that dementia was observed during life," warns Dennis Dickson of the Mayo Clinic in Jacksonville, who says he reviewed the neuropathology report.

"Mr. Williams was given a clinical diagnosis of (Parkinson's) and treated for motor symptoms. The report confirms he experienced depression, anxiety and paranoia, which may occur in either Parkinson's disease or dementia with Lewy bodies," Dickson said.

Fusiform gyrus key to understanding neuroanatomic basis of Capgras delusion

Thanks to Doug Shevlin, MD (pictured with crawdaddy) for steering me toward this TED talk by neuroscientist Vilayanura Ramachandran, MD, PhD. Dr. Ramachandran discusses the neuroanatomical substrate of the Capgras delusion, a neurological deficit about which I have blogged before. Dr. Ramachandran explains that the origin of this fascinating deficit stems from a severing (typically resulting from a stroke or neurodegenerative disorder) of the connection between the fusiform gyrus (the face perception area of the brain) and the amygdala (which gages the emotional significance of a perception). Good stuff....  including the crawdaddy.

Estelle Getty suffered from Lewy Body Disease

Here's an article describing today's passing of Estelle Getty, 'The Golden Girls' actress.

The Capgras Delusion in Dementia with Lewy Bodies

Southern Illinois University medical students Sameer Vohra and Teschlyn Woods were discussing Dementia with Lewy Bodies today and mentioned that Capgras syndrome can sometimes be a manifestation of this particular type of dementia. I had never heard of Capgras syndrome, but they explained it to me. Here’s what Wikipedia has to say about it:

"The Capgras delusion (or Capgras's syndrome) is a rare disorder in which a person holds a delusional belief that an acquaintance, usually a spouse or other close family member, has been replaced by an identical looking imposter.... It can occur in acute, transient, or chronic forms.
The delusion is most common in patients diagnosed with schizophrenia, although it can occur in a number of conditions including after brain injury and dementia. Although the Capgras delusion is commonly called a syndrome, because it can occur as part of, or alongside, various other disorders and conditions, some researchers have argued that it should be considered as a symptom, rather than a syndrome or classification in its own right."

It is named after Joseph Capgras (1873-1950), a French psychiatrist who first described the disorder in a 1923 paper by Capgras and Reboul-Lachaux. Here’s the link to the Wikipedia site describing the Capgras delusion:
http://en.wikipedia.org/wiki/Capgras_delusion

Final posting on the JNEN review article

The bottom line here is that although PD, DLB, and MSA are all synucleinopathies, they differ from one another in terms of composition of the inclusions. And, even among different patient there are differences in protein compostion of each inclusion (i.e., not all brainstem Lewy bodies are created equal). These are very complex issues that are far from being understood.

Yet more on the JNEN review article

Regarding brainstem Lewy bodies, here's something interesting from the article: "The ultrastructural similarities among filaments in LBs [Lewy bodies], pale bodies, and perikaryal threads prompted the hypothesis that AS [alpha-synuclein] perikaryal threads are an early stage of filament assembly that may then progress to pale bodies and, finally, to classic LBs."

Protein aggregation in the synucleinopathies

The current issue of the Journal of Neuropathology and Experimental Neurology has a review article about alpha-synuclein aggregation mechanisms in the major synucleinopathies: Parkinson's disease, Dementia with Lewy Bodies, and Multiple System Atrophy. The article was written by Drs. Katrin Beyer and Aurelio Ariza from Barcelona, Spain. I'll have more to say about this article in future posts.