The evidence implicating viral infection with neuronal damage is interesting and significant, but the authors need to be more careful in their application of the data to human neurological diseases. They mention that their results might help explain parkinsonisms, such as von Economo’s encephalitis, which is the illness described in Oliver Sacks’s book Awakenings, and the movie of the same name starring Robin Williams and Robert De Niro. The authors mention that the high prevalence of von Economo’s encephalitis after World War I has led some to link it to the 1918 influenza epidemic and refer readers to quarter-century-old papers. They then suggest that their study offers an explanation for this link. But the epidemic of von Economo’s encephalitis began in 1915. Von Economo described it in 1917. Recently it has been linked to streptococcal infection. So the link emphasized in this paper is a big stretch.

The authors also need to be a bit more careful in linking their data to a hit-and-run autoimmune mechanism. They state, “we show the virus is gone from the brain in 21...  Read more

The evidence implicating viral infection with neuronal damage is interesting and significant, but the authors need to be more careful in their application of the data to human neurological diseases. They mention that their results might help explain parkinsonisms, such as von Economo’s encephalitis, which is the illness described in Oliver Sacks’s book Awakenings, and the movie of the same name starring Robin Williams and Robert De Niro. The authors mention that the high prevalence of von Economo’s encephalitis after World War I has led some to link it to the 1918 influenza epidemic and refer readers to quarter-century-old papers. They then suggest that their study offers an explanation for this link. But the epidemic of von Economo’s encephalitis began in 1915. Von Economo described it in 1917. Recently it has been linked to streptococcal infection. So the link emphasized in this paper is a big stretch.

The authors also need to be a bit more careful in linking their data to a hit-and-run autoimmune mechanism. They state, “we show the virus is gone from the brain in 21 days” and then suggest that this absence implicates a hit-and-run mechanism of neuronal damage. It would have been better for them to say “we were unable to detect the virus 21 days after infection.” It has become clear over the past three decades that infectious agents may persist cryptically within their hosts far longer than is suggested by techniques that measure the conspicuous first flush of infection. This tendency to invoke a hit-and-run mechanism without adequately excluding low-level persistence is a general problem in the study of immunologically mediated diseases because it has led to a tendency to accept too quickly mechanisms of infectious triggers of immunological damage when evidence does not exclude damage induced by cryptic persistent infection. The authors didn’t need to make the claim that the virus was gone. Rather, they need only to make the point that their assays did not detect the virus.

View all comments by Paul W. Ewald

This work makes several interesting points and raises important questions. It puts us on notice that, like the flu epidemic of 1918, an H5N1 epidemic could potentially cause immediate or delayed parkinsonism in a significant part of the population. It demonstrates yet another example of how neuron damage can drive downstream protein aggregation. Also, if uncommon flu strains such as H5N1 can damage dopaminergic neurons, it is worth considering whether common flu strains that spread through the population each year also damage dopaminergic neurons. If so, flu viruses may contribute more to the development of parkinsonism, or perhaps even Parkinson disease, than we currently appreciate.

View all comments by Russell Swerdlow