Gulf War and Health Volume 7: Long-Term Consequences of Traumatic Brain Injury (2009) / Chapter Skim
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7 NEUROLOGIC OUTCOMES
7 NEUROLOGIC OUTCOMES
Pages 197-264
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From page 197... ...
note that TBI "accounts for 20% of symptomatic epilepsy in the general population and 5% of all epilepsy." Primary Studies The committee identified 10 primary studies that examined the association of TBI with seizures: six studies of military populations with penetrating head injuries and four of civilian cohorts with closed head injuries. See Table 7.1 for a summary of the primary studies.
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From page 198... ...
conducted a conditional cohort study of 500 head-injured men admitted within 3 days of injury into the Military Hospital for Head Injuries, Oxford. Information was collected on amnesia, electroencephalographic findings, personal and family history, cerebrospinal fluid (CSF)
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From page 199... ...
. As part of the Rochester Epidemiology Project, medical records containing physician diagnoses of TBI were linked to later medical records documenting unprovoked seizures in the study interval and compared with records of those who did not sustain TBI.
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From page 200... ...
Jennett and Lewin (1960) studied 1,000 patients who sustained nonmissile head injuries and were consecutively admitted to the Radcliffe Infirmary, Oxford, in 1948–1952.
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From page 201... ...
conducted a conditional cohort study of the occurrence of epilepsy after penetrating head injury in WWII soldiers and found that 42% of 562 soldiers had had epilepsy by 5 years after the penetrating TBI. Four secondary studies assessed seizure rates in head-injured patients admitted into hospitals.
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Summary and Conclusion The committee reviewed 10 primary studies and 19 secondary studies of TBI and seizures. The secondary studies are largely supportive of the primary studies that indicate that brain injury is associated with seizure activity.
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NEUROLOGIC OUTCOMES 203 resulting in loss of consciousness or amnesia and the development of unprovoked seizures.
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From page 204... ...
at least 0.5 h of were children less unconsciousness than 15 years old or PTA 1,640 mild head injuries: no fracture but unconsciousness or PTA for less than 30 min Annegers et Retrospective Same as above, but Mild: LOC or Seizures Including children, Cumulative Children included in al., 1998 cohort new cases added amnesia for determined from adults: probability of risk estimate; results (4,541) for less than 30 min medical records Mild: SIR, 1.5 (95% unprovoked include children,
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From page 205... ...
and skull fracture (95% CI, 1.9–4.1) ; Kaplan-Meier different from followup of Severe: LOC or severe, SIR, 17.0 method adults' rates original cases amnesia for (95% CI, 12.3–23.6)
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From page 206... ...
; per 1,000 of excess event rate, 1.1 population per year Severe head injury: comparative incidence rate, 17.0 (95 in first PT year, 16.7 in years 1–5) ; excess event rate, 10 Annegers et Retrospective 692 patients in Head trauma Seizures Age-adjusted Age Included children al., 1995 cohort Olmsted County, determined from incidence rates of and adults MN, who medical records; acute symptomatic developed acute acute symptomatic post-TBI seizures, symptomatic post- seizures defined as 2.0 per 100,000 TBI seizures in occurring within 7 person-years (25- to 1955–1984 days of brain 34-year-olds)
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From page 207... ...
, Seizures Prevalence of No reference group; 1963 cohort veterans with head blunt (48%) determined with seizures: overall, no screening for injuries treated by Six categories: I, postal 30.6%; seizures preinjury seizure study author or two head blow without questionnaire lasting > 6 mo, 22%; disorder other NS and MS change; II, penetrating, 42.1%; Cohort may overlap assessed 7–8 years transient LOC; III, blunt, 16.4%; I, with Evans 13526 after injury focal brain injury 7.1%; II, 10.4%; III, 207
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From page 208... ...
, blast determined with seizures: overall, no screening for injuries treated at (12%) postal 19.7%; penetrating, preinjury seizure US Naval Hospital Five categories: I, no questionnaire 32%; blunt, 8%; disorder in Yokusaka or on scalp lacerations, no blast, 2%; I, 1%; II, Cohort may overlap US hospital ships, skull fracture; II, 1.7%; III, 1.2%; IV, with Caveness 13530 assessed 3–11 scalp lacerations, no 1.7%; V, 14% Inability to years after injury skull fracture; III, Seizure prevalence determine number linear skull fracture; increased with who may have had IV, depressed skull increasing duration their one and only fracture; V, brain of LOC and PTA seizure within first 6 penetration mo after TBI Phillips, 1954 Conditional 500 adult male Blunt head trauma Seizures 6% had seizure No controls; unclear cohort "military whether combat personnel" related; unclear admitted into interval between military hospital injury and seizures; for head injuries in inability to Oxford for head determine number injury with seizures persisting beyond 6 mo Russell, 1968 Conditional 185 patients Penetrating TBI Seizures 21.6 % had seizures No controls, but cohort followed > 10 combat-related; years after injury cohort not described
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From page 209... ...
describe onset of first persisting beyond 6 seizures after injury mo, but Salazar and Rish report that 43% of seizure patients in this cohort had their first seizure more than 1 year after injury NOTE: CI = confidence interval, GSW = gun shot wound, LOC = loss of consciousness, MS = mental status, NS = neurosurgeons, PT = posttrauma, PTA = posttraumatic amnesia, RR = relative risk, SIR = standardized incidence ratio, TBI = traumatic brain injury, VA = Department of Veterans Affairs, VHIS = Vietnam Head Injury Study, WWI = World War I, WWII = World War II.
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From page 210... ...
Gerber and Schraa (1995) conducted a prospective study of patients consecutively admitted into an ED because of mild TBI and compared them with a group that had orthopedic injuries and with uninjured controls.
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From page 211... ...
After adjusting for PTSD and depression, however, headache was the only postconcussion symptom significantly more frequently reported, and that was only in the group with LOC. That raises the question of whether postconcussion symptoms are caused by mild TBI or PTSD and depression, or both.
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From page 212... ...
The two groups were similar in most demographic characteristics although participants with concussion reported slightly lower education and were less likely to be currently married. The authors found no significant differences between subjects who had sustained head injuries with brief LOC and controls in occurrence of any headaches during the previous month (p = 0.92)
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From page 213... ...
(2007) used the RPQ to collect information on symptoms from 37 subjects presenting at the Christchurch, New Zealand, Hospital ED with mild TBI (GCS scores, 13–15 at first assessment with no consecutive scores below 13; PTA less than 24 hours; and no structural damage or skull fracture on head CT if obtained)
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From page 214... ...
Gerber and Schraa (1995) conducted a prospective study of 22 consecutively admitted patients who had mild TBI matched with orthopedically injured patients and uninjured controls to assess injury severity, symptoms, and disability.
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From page 215... ...
The rate of PCS in patients with moderate or severe TBI was not reported. Limitations of the study include the lack of faceto-face interviews of LLI patients and the counting of symptoms whether or not they predated injury or were related to a different cause.
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From page 216... ...
. The median number of symptoms endorsed at 1 year was five by those with severe TBI, two by those with moderate TBI, three by those with mild TBI, and two by controls.
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From page 217... ...
Six of the eight primary studies were restricted to those with mild TBI. One looked at symptoms reported by soldiers who had recently returned from Iraq and found that significantly more who had had LOC reported each of the nine common postconcussion symptoms; significantly more of those with an altered mental state but no LOC reported five of the nine symptoms (Hoge et al., 2008)
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From page 218... ...
found that over 15% of people hospitalized with TBI in surgical or neurosurgical departments endorsed new occurrence of headaches, dizziness, fatigue, memory impairment, and being bothered by noise or light. One secondary study that assessed mild TBI (Stulemeijer et al., 2006b)
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From page 219... ...
; reported symptoms with minor questionnaire, > 7 days, 21% vs 15% only nonhead injuries, the RPSQ, VAS (p = 0.15) ; any Mild TBI based on followed for 1 for determining dizziness, 62% vs 50% clinical assessment; year, who symptom (p = 0.02)
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From page 220... ...
of symptoms, because controls returned little possibility of questionnaires at 1 receiving monetary year compensation for postconcussion symptoms Masson et al., Prospective 231 head injured Mild head injury, Self-reported See Table 7.4 Cohort population1996 cohort; with various 141; moderate head functional status based; age and sex population-based degrees of head injury, 38; severe through face-to- distribution similar study in injury; 80 controls head injury, 52; all face interview in in all groups Aquitane, with LLI hospitalized hospital or Symptom rates France, designed Over 15 to under home, telephone include symptoms to determine years old interview, or unrelated to injury incidence of all mailed After 5 years, serious injuries questionnaire; following patients resulting in self-reported not included in final hospitalization functional status analysis: lower-leg or death assessed with injury, one died, 15 European Chart lost to followup; for Brain Injured mild head injury, Patients two died, 18 lost to Evaluation; followup; two overall outcome refused to assessed with participate; GOS moderate head injury, two died; severe head injury, 25 died McLean et al., Prospective 102 hospitalized Broad range of Head Injury At 12 mo after injury, Group TBI cases, controls 1993 cohort adult head injured severity Symptom head injured vs friend matched on excluded if they had patients, 102 Checklist controls: memory age, sex, pre-existing uninjured controls problems, 39% vs 5% education, conditions; head who were friends (p < 0.001) ; race injured cases
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From page 221... ...
; may be related to headache, 36% vs 35%; head injury or other fatigue, 47% vs 43%; injuries bothered by light, 21% vs 10%; anxiety, 33% vs 26%; insomnia, 27% vs 15% Gerber and Prospective 22 patients with Mild Injury severity, % of MTBI patients Controls Schraa, 1995 mild TBI matched symptoms, who volunteered matched on with orthopedically disability as symptoms at followup: age, sex, injured patients, measured with headache, 13.6; education uninjured controls structured dizziness, 0; fatigue, 0; interview, concentration symptom problems, 13.6; checklist memory problems, 13.6; irritability, 0 Orthopedic controls volunteered none of listed symptoms; 9.1% of controls volunteered irritability Heitger et al., Prospective 37 patients with MTBI PCS assessed See Table 7.3 Controls 221 2007 cohort mild closed head Patients asked if head with written individually
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From page 222... ...
Hoge et al., 2008 Retrospective 2,525 US Army MTBI as assessed Postconcussion See Table 7.2 TBI, symptoms self infantry soldiers with positive symptoms reported; assessed surveyed 3–4 mo responses to any of assessed with with questionnaire after return from following items on Patient Health 3–4 mo after deployment to questionnaires: Questionnaire deployment; 59% of OIF: 124 head "losing 15-item somatic all soldiers injured with LOC, consciousness symptom deployed to OIF, on 260 head injured (knocked out) ," severity scale duty completed with altered mental "being dazed, Five questions in questionnaire; status, 435 with confused, or ‘seeing addition to 7% of values for other injury, 1,706 stars,'" or "not questionnaire to some variables with no injury remembering the assess symptoms missing
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From page 223... ...
287 patients 18–60 years old who presented to ED with ankle or wrist distortion, assessed 6 mo after trauma NOTE: ED = emergency department, GCS = Glasgow Coma Scale, GOS = Glasgow Outcome Scale, LLI = lower-limb injury, LOC = loss of consciousness, MTBI = mild traumatic brain injury, OIF = Operation Iraqi Freedom, OR = odds ratio, PCS = postconcussion syndrome, PTA = posttraumatic amnesia, RHIFQ = Rivermead Head-Injury Follow-up Questionnaire, RPSQ = Rivermead Postconcussion Symptoms Questionnaire, RR = relative risk, TBI = traumatic brain injury, VAS = Visual Analogue Scale.
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From page 224... ...
At 1 year after injury, those with closed head injuries did not show signs of cognitive impairment but had residual deficits in eye and arm motor function. Secondary Studies The committee identified one secondary study that assessed the relationship between TBI and ocular and visuomotor function.
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From page 225... ...
found that at 6 months after injury, patients with closed head injuries showed deficits on several ocular and upper-limb visual motor measures. At 1 year after injury, those with closed head injuries did not show signs of cognitive impairment but had residual deficits in eye and arm motor function.
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From page 226... ...
226 TABLE 7.6 Ocular and Visual Motor Deterioration and TBI Health Outcomes or Comments or Reference Study Design Population Type of TBI Outcome Measures Results Adjustments Limitations Heitger et al., Prospective 37 mild closed- Mild closed Saccades, Sustained motor Controls matched 2006 cohort head-injury head injury oculomotor smooth impairment up to 1 with respect to age, patients from ED (GCS, 13–15) pursuit, upper-limb year sex, years of at Christchurch visuomotor function, formal education Hospital, New neuropsychologic Zealand tests; recovery assessed with RPSQ NOTE: ED = emergency department, GCS = Glasgow Coma Scale, RPSQ = Rivermead Postconcussion Symptoms Questionnaire, TBI = traumatic brain injury.
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From page 227... ...
Primary Studies The committee identified eight primary studies that assessed the relationship between TBI and a variety of endocrine disorders, including diabetes insipidus (DI) , GH insufficiency, and hypopituitarism (see Table 7.7 for a summary of the primary studies)
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From page 228... ...
(2004a) prospectively studied the effect of moderate or severe TBI on anterior pituitary dysfunction in 102 consecutive patients admitted into a neurosurgical unit in Beaumont Hospital in 2000–2002.
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From page 229... ...
At 3 months after injury, 6 of the 46 patients had anterior pituitary deficiencies; at 12 months after injury, no additional patients had 3 A GCS of 3–8 indicates a severe TBI or a grade III, while a GCS of 9–12 indicates a moderate TBI (grade II) , and a GCS of 13–15 indicates a mild TBI or grade I
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. Secondary Studies The committee identified four secondary studies that assessed the relationship between TBI and a variety of endocrine disorders, including DI, GH insufficiency, and hypopituitarism.
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From page 231... ...
The committee concludes, on the basis of its evaluation, that there is limited/suggestive evidence of an association between moderate or severe TBI and diabetes insipidus. Growth Hormone Insufficiency The committee identified five primary studies (Agha et al., 2004a, 2004b, 2005a, 2005b; Kelly et al., 2006)
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From page 232... ...
(2004a) prospectively studied the effect of moderate or severe TBI on anterior pituitary dysfunction in 102 consecutive patients and found that 18 had a GH response to the GST test of less than 5 μg/L; 11 of these patients failed the ITT or the arginine + GHRH test.
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From page 233... ...
of related to age, GCS controls controls had cortisol score, or presence of responses to GST of < other pituitary 450 nmol/L, 13 of hormone whom also failed ITT abnormalities or synacthen test Agha et al., Prospective Same population as Moderate, defined WDT; plasma, In acute phase, 22 Matched on age, Inclusion criteria: 2004b cohort Agha et al., 2004a as GCS score of urine osmolalities; (21.6%) patients sex, BMI severe or moderate 9–13 urine volume; developed DI TBI, age 15–65 Severe TBI thirst score; blood Seven of 102 patients years, at least 6 mo defined as GCS pressure; weight; who sustained after injury score of 8 or less plasma sodium moderate or severe TBI Exclusion criteria: had permanent DI pregnant women, (6.9%)
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From page 234... ...
in sex, BMI TBI; studied acutely, GCS score 3–13 acute phase; 5 at 6, 12 mo after recovered after 6 mo; 2 TBI; 27 healthy more patients controls developed deficiency; at 1-year followup, 5 had GH deficiency Herrmann et Cohort 76 patients with Severe, defined as Neuroendocrine 18 of 76 had pituitary No control group, no al., 2006 severe TBI, GCS score < 8; tests, including GH deficiency indication of discharged from mean, 4.4 ± 2.8; response to GHRH Six of 76 had GHD percentage of neurosurgery patients injured + arginine; TSH; (GH peak range normals outside departments in average of 22 ± free T4, T4, T3; [GHRH + arginine] , reference range Germany 10 mo before prolactin; 2.8–6.3 μg/L; GH peak study testosterone; range [ITT]
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From page 235... ...
severe, GCS < 9 mo 12 mo after trauma, 1 alcohol or drug TBI hospitalized in patient recovered; no abuse, prior severe Copenhagen Baseline, additional patients head trauma or University Hospital; stimulated found to have apoplexies, chronic 30 healthy volunteer hormone deficiencies use of controls; another 100 concentrations; Five of 46 had GH glucocorticoids healthy volunteer Synacthen-test deficiency at 12 mo Mean GH not controls for (acute + 6 mo) ; Four of 15 patients significantly Synacthen test ITT, GHRH + with severe TBI had different from arginine test (used hypotituitarism vs 1 of controls at 3, 12 mo; 235
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From page 236... ...
reference range NOTE: ACTH = adrenocorticotropic hormone, AVP = arginine vasopressin, BMI = body-mass index, CI = confidence interval, DI = diabetes insipidus, FSH = follicle-stimulating hormone, GCS = Glasgow Coma Scale, GH = growth hormone, GHD = growth-hormone deficiency, GHI = growth-hormone insufficiency, GHRH = growth-hormone releasing hormone, GST = Glucagon Stimulation Test, IGF-1 = insulin-like growth factor-1, ITT = insulin-tolerance test, QOL = quality of life, SHBG = sex-hormone binding globulin, SIADH = syndrome of inappropriate antidiuretic hormone secretion, TBI = traumatic brain injury, TSH = thyroid-stimulating hormone, WDT = water-deprivation test.
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From page 237... ...
Subjects included 548 veterans who served during 1944–1945 and were hospitalized during military service with diagnosis of nonpenetrating head injury; 1,228 subjects matched on education and age who had unrelated injuries served as controls. Medical records were abstracted in 1996 and 1997 to document details of the closed head injuries.
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From page 238... ...
Secondary Studies The committee identified nine secondary studies that assessed the relationship between TBI and AD. Schofield and colleagues (1997)
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From page 239... ...
conducted a case–control study to assess risk factors for AD. Participants were 40 patients with onset of dementia and 80 controls matched on age, sex, and race.
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From page 240... ...
found that "late maternal age at birth and a history of head trauma [were] associated with a statistically significant increase in the risk for AD in the absence of a family history of dementia." Summary and Conclusions The committee identified one primary study (Plassman et al., 2000)
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From page 241... ...
Studies suggested an association between mild TBI with LOC and dementia of the Alzheimer type, but mild TBI without LOC was not found to be strongly associated with dementia of the Alzheimer type. The committee concludes, on the basis of its evaluation, that there is sufficient evidence of an association between moderate or severe TBI and dementia of the Alzheimer type.
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From page 242... ...
and/or skull Cognitive Status fracture; severe:(TICSm) , LOC, PTA > 24 telephone DQ, h clinical assessment of AD diagnosed according to NINCDS ADRDA criteria NOTE: AD = Alzheimer disease, ADRDA = Alzheimer's Disease and Related Disorders Association, CI = confidence interval, DQ = dementia questionnaire, HR = hazard ratio, LOC = loss of consciousness, NINCDS = National Institute of Neurological and Communicative Disorders and Stroke, PTA = posttraumatic amnesia, WWII = World War II.
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From page 243... ...
noted that "professional boxers with multiple bouts and repeated head blows are prone to chronic traumatic encephalopathy." In reviewing the literature on DP in boxers, the committee recognized that there is a considerable difference between amateur boxing and professional boxing in measures to protect against head injury. In amateur boxing, bouts are usually limited to three rounds of 3 minutes each; gloves are typically larger, heavier, and more absorbent than those used by professional boxers (Stewart et al., 1994)
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From page 244... ...
In addition, the severity of head injury and the nature of repeated trauma were unknown. Secondary Studies The committee identified six secondary studies that evaluated the relationship between TBI and DP in boxers and soccer players.
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From page 245... ...
Autopsies revealed cerebellar damage, cortical damage and other scarring of the brain, substantia nigral degeneration, neurofibrillary tangles in the cerebral cortex and temporal horn areas, and abnormalities of the septum pellucidum. Summary and Conclusions The committee identified six secondary studies that assessed the relationship between boxing or repeated heading in soccer and DP.
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From page 246... ...
The autopsies revealed cerebellar damage, cortical damage, and other scarring of the brain; substantia nigral degeneration; neurofibrillary tangles in the cerebral cortex and temporal horn areas; and abnormalities of the septum pellucidum. Findings in professional boxers demonstrate an association with the development of DP; pathology study of brains of autopsied boxers also support these findings.
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From page 247... ...
. The authors noted that the "results suggest an association between head trauma and the later development of PD that varies with severity." Possible study limitations include the broad confidence intervals, the potential for underascertainment of mild TBI from medical records alone, and the possibility that patients with more severe TBI might be followed more closely in the medical system, a phenomenon that could lead to an earlier diagnosis of PD.
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From page 248... ...
An increased risk was observed in patients with mild TBI and LOC or with more severe TBI. The authors noted that the "results suggest an association between head trauma and the later development of PD that varies with severity." Goldman and colleagues (2006)
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From page 249... ...
family history of People with mild TBI of injury Mild trauma, no PD might not have sought increased risk of medical attention, thus PD would not be in system; Men, OR, 6.0 result would be (95% CI, 1.3–26.8) underascertainment of mild TBI; if distributed Women, NS equally in PD case, Age of onset > 71 controls, bias would be years, p = 0.02 (no toward finding no OR because of lack effect of mild TBI on of data on controls)
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From page 250... ...
CAPIT criteria Association stronger in monozygotic twins than in dizygotic twins In subanalysis of 18 pairs concordant for PD, twin with earlier PD onset more likely to have sustained head injury NOTE: CAPIT = Core Assessment Program for Intracerebral Transplantations, CI = confidence interval, LOC = loss of consciousness, NS = not significant, OR = odds ratio, PD = Parkinson disease, REP = Rochester Epidemiology Project, TBI = traumatic brain injury, WWII = World War II.
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From page 251... ...
The author found no correlation between onset or exacerbation of MS and TBI or lumbar disk surgery. Summary and Conclusion The committee identified one primary study and one secondary study of the relationship between TBI and MS.
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From page 252... ...
252 GULF WAR AND HEALTH increased risk of MS after head injury. Similarly, the secondary study (Kurland, 1994)
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From page 253... ...
No adjustments for other potential risk factors Limitation is mixed age group; ages 0–65+ years included Strengths of study include head injury, MS diagnoses made independently, so recall bias avoided Geographically defined but otherwise unselected population Analysis of long- and short-term risk of MS after TBI NOTE: CI = confidence interval, ICD = International Classification of Diseases, MS = multiple sclerosis, OR = odds ratio, TBI = traumatic brain injury.
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From page 254... ...
. The committee identified no primary studies and few secondary studies of the relationship between TBI and ALS, but it recognized the importance of evaluating the literature for this outcome because there has been a concern about a relationship of the disease to military service (IOM, 2006)
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From page 255... ...
Kurtzke and Beebe (1980) found a higher frequency of intracranial injury in ALS subjects than in controls and stated that "men dying of ALS more often had a history of injury 15 or more years before death than did the controls during the same period." The secondary studies generally found higher rates of ALS in the head-injured, but no studies that met the criteria of a primary study were identified.
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From page 256... ...
2004a. Anterior pituitary dysfunction in survivors of traumatic brain injury.
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From page 257... ...
1999. Postconcussive symptoms and posttraumatic stress disorder after mild traumatic brain injury.
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From page 258... ...
1995. Mild traumatic brain injury: Searching for the syndrome.
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From page 259... ...
2006. Neurobehavioral and quality of life changes associated with growth hormone insufficiency after complicated mild, moderate, or severe traumatic brain injury.
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From page 260... ...
Brain Injury 10(7)
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From page 261... ...
2006. Prevalence of anterior pituitary insufficiency 3 and 12 months after traumatic brain injury.
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From page 262... ...
2007. Long-term morbidities following self-reported mild traumatic brain injury.
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From page 263... ...
1988. Thyroid test abnormalities in traumatic brain injury: Correlation with neurologic impairment and sympathetic nervous system activation.
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