MILD TRAUMATIC BRAIN INJURY AND THE POSTCONCUSSIONAL SYNDROME DR ROBIN JACOBSON ROYAL COLLEGE OF PSYCHIATRISTS SEPTEMBER 2017

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1 MILD TRAUMATIC BRAIN INJURY AND THE POSTCONCUSSIONAL SYNDROME DR ROBIN JACOBSON ROYAL COLLEGE OF PSYCHIATRISTS SEPTEMBER 2017

2 DEFINITION OF MILD TBI ACRM (1993) A traumatically induced physiological disruption of brain function, with at least one of the following: Any period of LOC 30 min Any loss of memory for events immediately before or after the accident (PTA <24 h) Any alteration in mental state at the time of the accident (feeling dazed, disorientated or confused) Focal neurological deficit(s) that may or may not be transient GCS score after 30 min

3 DEFINITION OF MILD TBI WHO (2004) Mild TBI is an acute brain injury resulting from external physical forces. Confusion or disorientation LOC 30 min PTA 24 h And/or other transient neurological abnormalities such as focal signs, seizure and intracranial lesion not requiring surgery GCS score after 30 min post-injury or later on presentation for health care

4 SEVERITY OF TBI RUSSELL & SMITH (1961) Mild Moderate Severe Very Severe PTA <1hr 1-24hrs 1-7 days 8-28 days

5 SEVERITY OF TBI DSM-5 (2013) Mild Moderate Severe GCS LOC <30 min 30 min-24 hrs PTA <24hrs >24hrs 7 days >24 hours > 7 days

6 THE SPECTRUM OF mtbi IS VERY WIDE: GCS Category 0 GCS = 15 No LOC, no PTA = head injury, no TBI No risk factors Discharge Category 1 GCS = 15 LOC < 30 min, PTA < 1 h No risk factors CT recommended Category 2 GCS = 15 and risk factors present CT mandatory Category 3 GCS = LOC < 30 min, PTA < 1 h EFNS guidelines Vos et al, 2002 With or without risk factors CT mandatory

7 DAY-OF-INJURY CT SCAN ABNORMALITIES IN MTBI (COMPLICATED MTBI) GCS 15 5% 14-20% 13 30% Borg et al, 2004, WHO Task Force

8 TAMPERE UNIVERSITY ED COHORT RATES OF COMPLICATED MTBI (N=2766) GCS % abnormal CT head % % 13 52% Isokuortti et al, 2017

9 ARE INTRACRANIAL ABNORMALITIES RELATED TO CLINICAL OUTCOMES?

10 COGNITIVE OUTCOMES Those with intra-cranial abnormalities performed more poorly on neuropsychological testing (11 of 19 studies 58%) But only small to medium effect sizes Usually on few of the cognitive tests

11 FUNCTIONAL OUTCOMES In 4 of 13 studies, complicated MTBI patients had greater problems on: - Glasgow Outcome Scale - Functional Independence Measure - Global Adaptive Functioning Scale - Return to work Most studies, however, have not found a significant difference in functional outcomes.

12 ICD-10 POSTCONCUSSIONAL SYNDROME

13 Rivermead Post Concussion symptoms Questionnaire Compared with before the accident, do you now (i.e., over the last 24 hours) suffer from: Headaches Feelings of Dizziness Nausea and/or Vomiting Noise Sensitivity, easily upset by loud noise Sleep Disturbance Fatigue, tiring more easily Being Irritable, easily angered Feeling Depressed or Tearful Feeling Frustrated or Impatient Forgetfulness, poor memory Poor Concentration Taking Longer to Think Blurred Vision Light Sensitivity, Easily upset by bright light Double Vision Restlessness = Nil 1 = the same 2 = mild 3 = moderate 4 = severe

14 LEVIN ET AL 1987 J NEUROSURGERY, 66: A single uncomplicated minor HI produces no permanent disabling neurobehavioural impairment in the great majority of patients who are free of pre-existing neuropsychiatric disorder and substance abuse. "A subacute disturbance of attention, memory, and information-processing efficiency is common during the first few days after HI... By 1-3 months most patients recover to within the range of matched controls, but neurobehavioural deficits occasionally persist for longer in a minority. Subjective c/o's frequently occur at baseline and 1 and 3 months F-Up's, even in patients with recovered cognitive functioning."

15 LISHMAN (1988) Organic factors are chiefly relevant in the earlier stages, whereas longcontinued symptoms are perpetuated by secondary neurotic developments, often of a complex nature.

16 KING, 2003 When PCS persists, Psychological features will entirely account for the symptoms in some individuals. Organic or quasi-organic features will entirely account for the symptoms in others.

17 MCCREA: MTBI AND PCS, 2008 Post Concussional Syndrome is a neuropsychological disorder associated with the transient neurological effects of MTBI but maintained by a combination of psychological and social factors in the overall majority of cases.

18 MTBI RECOVERY BY 90 DAYS MCCREA ET AL 2003 Concussed vs Control Athletes Resolution of: PCS 7/7 Balance 3-5/7 Cognition 5-7/7 No difference between groups at 90/7. Acute disturbance, exponential recovery rate

19 MTBI PROLONGED RECOVERY MCCREA ET AL, 2013 Prolonged recovery (>7 days) in 10% concussed athletes Initial LOC, PTA, acute symptoms Worse initial cognitive function

20 MODERATORS OF NEUROPSYCHOLOGICAL OUTCOME Belanger et al (2005) Meta-analysis: 1463 MTBI pts & 1191 controls Effect size D = 0.54, moderate In unselected or prospective samples, no residual neuropsychological impairment by 90 days post-injury. (D= 0.04). In clinics and litigation samples, greater cognitive sequelae at 3 months (D= 0.74) Sampling methods important

21 PERSISTENT PCS, MTBI AND META-ANALYSIS Iverson (2010): Meta-analysis should not be used to unequivocally state that MTBI cannot cause long term problems in a minority.

22 PCS: DOES IT EXIST? Not in DSM-5? Not in ICD-11 Meares, 2011: Acute PCS not specific to mtbi (mtbi 43.3%; orthopaedic controls 43.5%). High base rates in general population (Powell, 2008) High rates in non-concussed school athletes (Iverson, 2015).

23 POST CONCUSSIONAL SYNDROME Commoner in women than men Pre-injury mental health problems a major risk factor Influenced by traumatic stress Persistent Sx at 1 or 3 months predict persistent Sx at 1 year Easy to misdiagnose in those with depression, anxiety, PTSD, chronic pain

24 PCS can be mimicked, magnified or masked by: Traumatic stress Anxiety Depression PTSD Chronic pain Sleep disturbance Social psychological factors at any point during recovery

25 PCS may be mimicked, magnified or masked by: Concussion TBI Vestibular damage Scalp, skull injury Headache

26 SYSTEMATIC REVIEW OF SELF-REPORTED PROGNOSIS IN ADULTS AFTER MTBI: RESULTS OF THE INTERNATIONAL COLLABORATION ON MILD TBI PROGNOSIS CASSIDY ET AL, 2014 The term postconcussion syndrome should be replaced with posttraumatic symptoms because they are common to all injuries

27 MISDIAGNOSIS OF THE PERSISTENT PCS IN DEPRESSION C. 90% of people with depression, with no prior head trauma, meet symptom criteria for a mild or greater form of ICD-10 PCS Iverson Archives of Clinical Psychology 21 (2006)

28 MISDIAGNOSIS OF THE PERSISTENT PCS IN PTSD Persistent PCS at 3 months after MTBI are not specific enough to be identified as a unique PCS and should be considered part of the hyperarousal dimension of PTSD MTBI predicted PTSD but not PCS Lagarde et al, 2014

29 PREDICTORS OF SUSTAINING A HEAD INJURY? COMPARED WITH AGE & SEX MATCHED CONTROLS Presence or risk of psychiatric disorder ADHD Adeyemo 2014, Biedermann, 2015 Alcohol abuse Previous head injury

30 PREDICTORS OF SUSTAINING AN MTBI Employment status - 57% of the Glasgow mtbi unemployed at time of injury Life Events - those with mtbi had twice as many life events in the year before injury as controls BDNF genotype met/met homozygous Thornhill at al. BMJ 2000; Fenton et al 1993 BJPsych; Dretsch et al Brain Behav 2016

31 PREDICTORS OF OUTCOME OF MTBI

32 WHITE MATTER, COGNITION, MTBI 53 pts with MTBI (GCS13-15) vs Controls 6 days FA VF VF FA in CC in left hemisphere 1 year FA VF normal FA = astrogliosis & axonal neurofilament compaction FA = myelin sheath damage Croall et al, 2014

33 REVIEW OF 50 DTI STUDIES IN MTBI (Wäljas et al, 2014) Findings Yes No Not Reported Abnormal White Matter 88% 12% --- Correlated With: Return to Work 0% 2% 98% Post-Concussion Symptoms 12% 6% 82% Cognitive Functioning 54% 8% 38% Mental Health Problems 6% 8% 86%

34 DTI & PCS AFTER MTBI: SYSTEMATIC REVIEW TO MAY 2016 Fractional Anisotropy, mean and radial diffusivity associated with Development of PCS Severity of PCS Corpus callosum vulnerable Khong et al, 2016 (10 studies)

35 PREDICTORS OF OUTCOME AFTER TBI: CONNECTIVITY DEFAULT MODE NETWORK 23 patients with mtbi vs 18 age matched healthy controls Connectivity posteriorly correl w. impaired cognition Connectivity anteriorly correl w. post traumatic sx Zhou et al Radiology, 2012, 265,

36 DTI FOR OUTCOME PREDICTION IN MTBI: A TRACK-TBI STUDY Predictors of 6 month outcome (GOS-E, RPQ-13) Severely reduced FA OR 3 Neuropsychiatric history OR 4 Years education OR 3 MRI surpassed all other predictors for 3- and 6-month outcome prediction in those with no h/o psych or substance abuse. Yuh et al 2014

37 CHALLENGES OF DTI To identify Traumatic Axonal Injury in an individual Specificity Clinical significance Relationship to Cognition and behaviour Outcome

38 WHITE MATTER ABNORMALITIES FOUND IN: Depression ADHD Dyslexia and LD Adolescent substance misuse Hypertension Cigarette smokers Obesity and metabolic syndrome Some healthy controls

39 MORE INTELLIGENT MEN SHOWED HIGHER FA IN THE GENU AND BODY OF THE CORPUS CALLOSUM DUNST ET AL, 2014

40 NOT ALL DTI STUDIES ARE POSITIVE

41 PROSPECTIVE BIOPSYCHOSOCIAL STUDY OF PERSISTENT PCS FOLLOWING MTBI (WALJAS ET AL, 2015, J. NEUROTRAUMA) Sample not involved in litigation N = 126, Control Group DTI, cognitive testing and questionnaires at 1 month and 1 year post-injury DTI abnormalities in 50% of the sample (12% of controls)

42 WALJAS ET AL, 2015 Abnormalities on DTI and MRI NOT sig. assoc. with greater PCS Abnormalities on DTI and MRI NOT sig. assoc. with worse neuropsychology Prior mental health problems & extra-cranial injuries predict PCS at 1 month PCS at 1 month predict PCS at 1 year Depression predicts PCS at 1 month & 1 year.

43 PERSISTENT SYMPTOMS AFTER MTBI COHORT OF TATOR 221 patients referred 1997 to 2013 to neurosurgeon majority (2/3) sports injuries many with 3 or more concussions many with chronic PCS Tator et al. 2011; 2016; Hiploylee et al. 2017

44 TATOR ET AL Follow up (55% response rate) Excluded contusions, haemorrhages, TOMM +ve cases, litigants None recovered who had PCS> 3 years Best predictor of recovery = number of PCS

45 A BIO-PSYCHOSOCIAL CONCEPTUALISATION OF OUTCOME FROM mtbi (IVERSON, 2011) IVERSON IS THE LEAD AUTHOR

46 BIO-PSYCHOSOCIAL CONCEPTUALISATION OF OUTCOME: THE BELFAST STUDIES OF MILD AND MODERATE TBI FENTON, MCCLELLAND, MONTGOMERY, MACFLYNN, RUTHERFORD

47 BELFAST STUDIES OF MILD AND MODERATE TBI G FENTON, R MCCLELLAND, A MONTGOMERY, G MACFLYNN, W RUTHERFORD Post Concussional Symptoms (PCS) Time 0 6 weeks 6months 44% 42% 54%

48 PATTERNS OF RECOVERY AND BRAINSTEM DYSFUNCTION IN MILD HI (MONTGOMERY ET AL, 1991) ABNORMAL BAEPs 1. ACUTE GROUP - 52% Day 0 6 weeks Recovery within 6 weeks 54% 6% 2. CHRONIC GROUP - 16% Symptoms persist over 6 months 100% 100% 3. SYMPTOM EXACERBATION GROUP - 32% Symptoms from 6 weeks to 6 months 12.5% 0% BAEP = Brainstem auditory evoked potential

49 MEDICO LEGAL ASPECTS ASSESSMENT OF PTA EFFORT TESTS THE GCS 15 SEVERE TBI OR SUBTLE BRAIN DAMAGE

50 DEFINITION OF PTA Disorder of episodic memory Other abnormalities: - confusion - disorientation - agitation - semantic errors - impaired backward digit span - verbal fluency - Slowed RT Wilson et al, 1992; Ahmed et al 2000; Marshman et al, 2013

51 VALIDITY OF PTA 1: NAN RECOMMENDATIONS. RUFF ET AL, 2009 PTA vs LOC Recall vs reconstruction PTA vs Psychogenic amnesia Alcohol/drug intoxication Severe physical injury + pain bias recall Opiates and benzodiazepines Timeline of events eg sleep Late onset amnesia is not PTA

52 VALIDITY OF PTA 2: Definite vs patchy gaps Course of islands of memory Specific vs general memories Abruptness of ending Learned responses in repeated testing (Friedland & Swash, 2016)

53 VALIDITY OF PTA 3: KEMP ET AL, % of orthopaedic and non-head injured patients report PTA >24 hours (Rivermead Protocol) Risk factors: Opioids, surgery, anxiety (57.5% variance) I predictive factor required for apparent PTA Mimicked PTA = 4 96hrs

54 VALIDITY OF PTA 4: PTA major estimator of severity but it should not necessarily be the sole determining factor The validity of PTA as the sole measure of severity of TBI has never been objectively tested King et al, 1996; Friedland & Swash, 2016

55 PTA IS RETROSPECTIVE ASSESSMENT RELIABLE? - 1 Severe TBI Good correlation retro and prospectively (GOAT 0.87) years later Mean pro-pta = 34 days (2-185) Mean retro-pta = 39 days (1-244) McMillan et al, 1996

56 PTA IS RETROSPECTIVE ASSESSMENT RELIABLE? -2 Minor TBI Good correlation retro and pro in 75% at 1-3 months 1 st and 2 nd retrospective PTAs differ in 11% Discrepancies are longer PTAs Gronwall & Wrightson (1980)

57 PTA IS RETROSPECTIVE ASSESSMENT RELIABLE? - 3 Inter-rater reliability = 0.79, but lower (0.59) for PTA < 24 hours or for long delay btw assessments (0.64) (King et al, 1997) After 5 years, retrospective PTA unreliable (does not correl with cognitive deficits. Ashla et al, 2009)

58 UNDER-ESTIMATION OF PTA Islands of memory Confabulation False memories Reconstruction of events from accounts by others

59 BASE RATE OF FAILED EFFORT IN THE MEDICO- LEGAL CONTEXT Mittenberg et al: Survey of 388 members of the American Board of Clinical Neuropsychologists, % of personal injury claims (n=6371) thought to have probable malingering.

60 BASE RATE OF FAILED EFFORT IN THE MEDICO-LEGAL CONTEXT: ESTIMATES OF MALINGERING mtbi 40% (range 15-64%). chronic pain 31% fibromyalgia/chronic fatigue 35% moderate-severe TBI 26% neurotoxic exposure 26% electrical injury 22% Mittenberg et al, 2002; Larrabee, 2003.

61 MEASUREMENT OF EFFORT Stand alone tests WMT, TOMM Embedded measures

62 GREEN ET AL, 2001 Effort has a greater effect on test scores than severe brain injury in compensation claimants

63 THE CONCEPT OF THE GCS 15 SEVERE TBI HAS BEEN PROMOTED IN THE MEDICO-LEGAL CONTEXT DAI found in mild TBI - Neuropathology, biomarkers & SWMRI LOC & GCS poor guides to DAI PTA > 24 hrs & presence of chronic symptoms of DAI prove severe TBI = DAI = permanent symptoms and disability