Cerebrocerebellar hypometabolism associated with repetitive blast exposure mild traumatic brain injury in 12 Iraq war Veterans with persistent post-concussive symptoms
Introduction
There is intense controversy regarding the etiology, course, and treatment of persistent somatic, cognitive, and behavioral symptoms experienced by many military personnel and Veterans following exposure to blast concussion (Connors et al., 2009, Eibner et al., 2009, Hoge et al., 2009, Sigford et al., 2009). It is universally accepted that blast exposed personnel frequently meet American Congress of Rehabilitation Medicine (ACRM) criteria for acute mild traumatic brain injury (mTBI) (Kay et al., 1993). But the term “mTBI” increasingly has been applied to a very different chronic post-concussive syndrome of subtle cognitive deficits, headache, tinnitus, sleep disruption, daytime fatigue, irritability and other symptoms that persists for months and often years after the blast-induced acute mTBI. Whether these chronic symptoms reflect persistent structural or functional brain damage is not clear. An epidemiologic study in military personnel found that chronic post-concussive symptoms (except for headache) were more correlated with posttraumatic stress disorder (PTSD) and depression (Schneiderman et al., 2008). These data would argue against persistent brain damage providing a neurobiologic basis for blast-related chronic post-concussive symptoms. On the other hand, many clinicians are convinced that war combatants’ chronic post-concussive symptoms suggest real albeit subtle persistent brain damage (Connors et al., 2009, Eibner et al., 2009, Ruff et al., 2008, Schneiderman et al., 2008, Sigford et al., 2009).
Demonstrating the presence of regional brain hypometabolism by fluorodeoxyglucose positron emission tomography (FDG-PET) in combat Veterans with chronic post-concussive symptoms years after their last blast exposure mTBI, compared to a control group, would inform this debate. Here we report consistent regional hypometabolism in infratentorial and medial temporal brain regions in a sample of Iraq war combat Veterans with multiple episodes of blast exposure mTBI and persistent post-concussive symptoms.
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Participants
The Veterans Affairs Puget Sound Health Care System (VAPSHCS) and University of Washington (UW) institutional review boards approved all procedures and all the participants provided written informed consent before enrollment into the study. The mTBI Veteran participants were a convenience sample of 13 male Veteran warriors recruited from the VAPSHCS, all of whom had documented hazardous duty experience in Iraq with the US Armed Forces and had reported experiencing at least one blast exposure in
Demographic characteristics
One mTBI Veteran participant was dropped from the study due to TOMM scores suggesting poor effort. His scores and imaging findings are not included in the results presented here. The remaining 12 mTBI Veteran participants were 32.0 ± 8.5 years of age (range 24–49 years) at the time of study enrollment. They had 13.8 ± 1.9 years of education (range 11–16 years). The cognitively normal community volunteer controls were 53.0 ± 4.6 years of age (range 49–56 years) and had 15.5 ± 2.0 years of education (range 12–19
Discussion
This is the first report of FDG-PET in military blast-exposure mTBI. We demonstrated consistent regional hypometabolism in infratentorial (cerebellum, vermis, and pons) and medial temporal brain regions in Iraq combat Veterans with multiple episodes of blast-related mTBI. These participants also exhibited subtle impairments in complex information processing, with mild reductions in verbal fluency, processing speed, and aspects of attention and working memory. These findings suggest the
Conflict of interest statement
The authors declare that there are no conflicts of interest.
Acknowledgments
This material is based upon work supported, in part, by the Northwest Network Mental Illness, Research, Education, and Clinical Center (MIRECC) and Office of Research and Development Medical Research Service, Department of Veterans Affairs; by grants P50 AG05136, K08 AG023670, and R01 NS045254 from the National Institutes of Health; and by a grant from an anonymous foundation.
References (47)
- et al.
The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research
Psychiatry Res.
(1989) - et al.
Genotyping and sequence analysis of apolipoprotein E isoforms
Genomics
(1988) - et al.
The validity of the PTSD checklist as a measure of symptomatic change in combat-related PTSD
Behav. Res. Ther.
(2001) - et al.
Computerized neurocognitive scanning: I. Methodology and validation in healthy people
Neuropsychopharmacology
(2001) - et al.
Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI
J. Lipid. Res.
(1990) - et al.
Psychosocial recovery after head injury
Arch. Phys. Med. Rehabil.
(1993) - et al.
Cerebellar injury: clinical relevance and potential in traumatic brain injury research
Prog. Brain Res.
(2007) - et al.
Heavy neurofilament accumulation and alpha-spectrin degradation accompany cerebellar white matter functional deficits following forebrain fluid percussion injury
Exp. Neurol.
(2007) - et al.
Benton Controlled Oral Word Association Test: reliability and updated norms
Arch. Clin. Neuropsychol.
(1996) - et al.
Functional topography in the human cerebellum: a meta-analysis of neuroimaging studies
Neuroimage
(2009)