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Shell shock remains 'unsolved'

Monday 19 January 2015

The Mail Online tells us shell shock has been "solved" after scientists claimed they have pinpointed the brain injury that causes pain, anxiety and breakdowns in soldiers.

The Mail's claim is prompted by a study that carried out autopsies on five military veterans who had a history of blast exposure to see what type of brain damage this might have caused.

Four out of five of these people showed signs of what is called diffuse axonal injury, where there is damage to the long nerve fibres that carry electrical signals throughout the brain. This nerve fibre damage seemed to have accumulated in "honeycomb" patterns.

However, we cannot conclude with any degree of certainty that blast injury was the direct and only cause of this damage, as these results are clouded by several factors.

Three of the five veterans died from an opiate overdose. People without a military background who died from an overdose also showed this nerve fibre damage, as did people who had suffered other types of brain injury, such as from a traffic accident – albeit without the honeycomb pattern.

This means it is difficult to know how much other factors contributed to this nerve fibre damage. In short, shell shock has not been "solved", as the Mail Online would have us believe.

Where did the story come from?

The study was carried out by researchers from the Johns Hopkins University School of Medicine in the US.

Funding was provided by the Johns Hopkins Alzheimer's Disease Research Center, the Kate Sidran Family Foundation, and the Sam and Sheila Giller family.

The study was published in the peer-reviewed medical journal, Acta Neuropathologica Communications on an open-access basis, so it is free to read online or download as a PDF.

The Mail Online coverage does not acknowledge that we cannot draw any firm conclusions on cause and effect from the results of this small study.

Claims stating shell shock has been "solved" are simplistic and cannot be supported by the results of such a small study, where multiple confounding factors are involved.

What kind of research was this?

This was a laboratory study that aimed to look at the brain changes that may occur from exposure to blast injury during military deployment.

The researchers say there are thought to be 250,000 veterans of conflicts in Iraq and Afghanistan with traumatic brain injury, many resulting from a blast.

This a complex form of injury said to incorporate "the direct effects of overpressure wave (primary injury), the gunshot-like effects of debris and shrapnel showering the head (secondary injury), the fall impact from translocation of the body by the overpressure wave (tertiary injury), as well as flash burns from the intense heat and asphyxiation or inhalation injuries".

Though there is a 100-year history of blast injuries, starting with those resulting from artillery shelling during the First World War, there is still a lack of understanding of the actual physical damage and injury it causes the brain.

Recent animal studies suggest these blasts cause what is called diffuse axonal injury. Diffuse means the injury is spread throughout the brain, rather than being isolated to one specific area.

It usually results from acceleration or deceleration forces moving the brain within the skull, similar to what may occur through vigorous shaking, which causes tearing injuries to the long nerve fibres (axons) that transmit signals throughout the brain.

Diffuse axonal injury is one of the most common types of traumatic brain injury, and effects can range from concussion to coma and death. 

This study conducted autopsies of veterans who had a history of blast injury to see whether there was any evidence of diffuse axonal injury.

What did the research involve?

The study included five male veterans with a history of blast injury who died at an average age of 28. Three died from an opiate or alcohol overdose. Similarly aged control subjects used as a comparison included:

  • six people who died from an opiate overdose (four females, two males)
  • six people who died from a lack of oxygen to the brain (three males, three females)
  • five people who died from another type of traumatic brain injury, such as falls or road traffic accidents (all male)
  • seven people who died with no history of traumatic brain injury, overdose or oxygen starvation

The researchers carried out brain autopsies on these people, particularly looking for evidence of amyloid precursor protein (APP), which is said to accumulate when there is diffuse axonal injury.

What were the basic results?

The researchers found four out of five of the blast injury cases showed evidence of APP accumulation in the nerve fibres in various parts of the brain, most predominantly in the frontal area.

These areas of damage were described to have formed into irregularly shaped "honeycomb" patterns.

The one person who did not show these abnormalities was said to have died from a gunshot wound to the head, and had a history of exposure to several IED attacks.

Three out of four of these cases with APP accumulation in the nerve fibres died from an opiate overdose. When compared with six non-military people who also died from opiate overdose, five of these controls were also found to have a few APP abnormalities, but they were significantly fewer in number.

Also, compared to the war veterans, none of these controls displayed the same "honeycomb" distribution of nerve fibre damage. 

In the controls who also died from traumatic brain injury, but not military related, these people showed quite a different pattern of nerve fibre damage from both the veterans and those who had died from an opiate overdose.

Their nerve fibre abnormalities tended to be "thick with prominent undulations and bulbs", while the non-military controls who died from an opiate overdose tended to have thin, straight abnormalities.

The controls who died as a result of a lack of oxygen to the brain showed quite variable APP accumulation – two showed APP abnormalities, four did not.

The controls without any history of traumatic brain injury, oxygen starvation or overdose did not show any APP abnormalities at all.

How did the researchers interpret the results?

The researchers say that: "Our findings demonstrate that many cases with history of blast exposure are featured by APP [nerve fibre damage] that may be related to blast exposure, but an important role for opiate overdose, [lack of oxygen to the brain before death], and concurrent blunt traumatic brain injury events in war theatre or elsewhere cannot be discounted."


This research aimed to shed light on the type of brain damage that blast exposure during military conflict may cause.

Previous research suggested blast exposure can cause diffuse axonal injury, where the forces acting upon the brain cause tearing and damage of the long nerve fibres that connect different parts of the brain.

This study found some supportive evidence suggesting this might be the case. Four of the five veterans with a history of blast injury did show this type of nerve fibre damage.

Researchers also observed a distinctive "honeycomb" pattern of nerve fibre damage, which was not present in other controls.

However, it cannot be concluded with much certainty that blast injury was the direct and only cause of this damage, as these results are clouded by several factors. Three of these five veterans died from an opiate overdose.

Non-military people who also died from an overdose still showed this nerve fibre damage, albeit in a different pattern. Similarly, people who suffered other types of traumatic brain injury also had this type of nerve fibre damage, though again with a different pattern.

Therefore, as the researchers acknowledge, it is difficult to rule out the influence that opiate overdose, lack of oxygen to the brain around the time of death, and other non-blast trauma may have had upon these brain changes in this military sample.

It is also not known whether these nerve fibre injuries had any effect on the person's subsequent health and brain function, or whether the injury was related to their cause of death in any way.

This is likely to depend on the severity of the brain damage: as is already recognised, diffuse axonal injury can encompass a wide extent of brain damage, from mild concussion to death.

The reliability of this study's conclusions would be improved if the results were replicated in a larger number of people, or in studies that better accounted for the wide range of other confounders (such as associated injuries or causes of death) that could explain the difference observed.

Although this study is of interest, the small sample sizes examined here – both the military personnel and the various control groups – make it difficult to draw any firm conclusions about the type of damage and subsequent health effects that may result from blast injuries during military conflict.

If you serve, or have served, in the armed forces and think your experiences have taken a psychological toll, there is help and support available. Read more about accessing healthcare for military personnel and veterans.

Analysis by Bazian
Edited by NHS Website

Links to the headlines

Shell shock solved: Scientists pinpoint brain injury that causes pain, anxiety and breakdowns in soldiers

Mail Online, 16 January 2015

The mystery of shellshock solved: Scientists identify the unique brain injury caused by war

The Independent, 15 January 2015

Links to the science

Ryu K, Horkayne-Szakaly I, Xu L, et al.

The problem of axonal injury in the brains of veterans with histories of blast exposure

Acta Neuropathological Communications. Published online November 25 2014