This document summarizes a presentation on neuropsychiatric aspects of head injury. It begins with an introduction discussing the prevalence of head injuries. It then covers the history of understanding head injuries, comparative diagnostic classifications, epidemiology, types and pathophysiology of head injuries including acute and chronic behavioral consequences. The presentation also discusses clinical features such as cognitive impairment, personality changes, mood disorders, anxiety, aggression and psychosis. It concludes with discussing prognosis and predictors of outcome following head injury.

1. Neuropsychiatric aspects of HEAD INJURY Speaker: Dr. Santanu Ghosh, Post Graduate student, Psychiatry. Moderator: Dr. J.N. Das, Asstt. Professor, Psychiatry. Assam Medical College, Dibrugarh. 1

2. Outline of presentation: Introduction History Comparative Nosology Epidemiology Types of head injury Pathophysiology Clinical features Prognosis Outcome Management Take home message Bibliography 2

3. Introduction: Head injuries are unfortunately common in today's world due to mass use of motor vehicles and widely misused alcohol. The peak incidence is between the ages of 15-24 & improved medical care has resulted in large numbers of individuals surviving with neuropsychiatric consequences. Most head injury survivors who present to psychiatric services have emotional symptoms & personality changes. A smaller number manifest serious and lasting cognitive sequelae such as apathy, disinhibition & amnesia. There are also important acute psychiatric effects of head injury. 3

4. History: Earliest written evidence of TBI found on Edwin Smith Papyrus 5000 years ago. The Hippocratic Corpus included treatise on head injury with thoughtful comments on skull #, delirium, seizure, coma. Adolf Mayer introduced the term ‘ traumatic insanity’ 4

5. Comparative Nosology: DSM-IV : Mental & behavioral problems due to traumatic brain injury. ICD-10: Other conditions associated with mental & behavioral disorders— -Chapter: XIX: S06- Intracranial injury 5

6. Epidemiology: 500,000 new cases of TBIs occur in the US each year.* 50,000 Deaths 235,000 Hospitalizations 80%-mild, 10%-moderate, 10%- severe TBI M:F=2-3:1 6 INCIDENCE: Closed TBI- 200/100,000 population Penetrating TBI- 12/100,ooo population

9. PATHOPHYSIOLOGY 9

10. Neuropathological classification of TBI: Focal lesions: Extracerebral hemorrhage: epidural,subdural,subarachnoid Intracerbral hemorrhage Focal ischemic lesion Diffuse lesions: Diffuse axonal injury. Diffuse ischemic damage. 10

15. Abnormality in cholinergic neuronal activity.

16. Abnormality in ascending biogenic amine pathway.14

17. (Pathology- contd….) Excitotoxic injury Glutamate Pathway: Na+ & cl- influx Cellular Edema Ca2+influx Expression of early transcription factors, acute phase proteins, caspases, proteolytic enzymes Neuronal apoptosis 15

18. (Pathology- contd….) Clinical evidences: CSF finding of glutamate concentrations are significantly elevated for several days after TBI. Glutamate antagonists have shown beneficial effects in experimental models of TBI. 16

20. (Pathology- contd….) Clinical evidences: A reduction in cholinergic transmission in hippocampal & neocortical areas observed after TBI . Dysfunction of the septohippocampal cholinergic pathway is observed in experimental models which has significant role in posttraumatic cognitive & behavioral deficits. 18

21. (Pathology- contd….) Ascending biogenic amine: 19 Synaptic conc. Of biogenic amine neurotransmitter Downregulation of biogenic amines Depressive symptoms

23. Serotonegic & noradrenergic metabolites in CSF.

24. Dysregulation of mesolimbic & mesocortical dopaminergic pathway give rise to manic & hypomanic syndromes.20

25. Lobe Functions(Cerebral): 21 Parietal lobe Dominant side: Non-dominant side: - Calculation - spatial orientation - Language - constructional skills - Planned movement - Appreciation of size, shape, weight, texture Frontal lobe: - Personality - Emotional response - Social behavior

26. Contd… 22 Occipital lobe: - Analysis of vision Temporal lobe Dominant side Non-dominant side -Auditory perception -Auditory perception -Speech, language -Music, tone sequence -Verbal memory -Non-verbal memory -Olfaction

27. Neuropsychiatric Syndromes Associated With Neuroanatomical Lesions Lateral orbital pre-frontal cortex - Irritability - Impulsivity - Mood lability - Mania Anterior cingulate pre-frontal cortex - Apathy - Akinetic mutism Dorsolateral pre-frontal cortex - Poor memory search - Poor set-shifting / maintenance Temporal Lobe - Memory impairment - Mood lability - Psychosis - Aggression Hypothalamus - Sexual behavior - Aggression 23

28. CLINICAL FEATURES: 24

30. Amnestic disorder - Transient/ chronic.

31. Dementia.

32. Personality change – -Labile -Disinhibited -aggressive -apathetic -Paranoid -combined -unspecified 25

34. Psychotic disorder: - with delusion - with hallucination CTP,8TH ed,page-390 26

36. Retrograde amnesia (RA): Period between the last clearly recalled memory prior to the injury & the injury itself. Dense amnesia lasting seconds & minutes.27

38. Associated with 10-65% mortality

39. Variable confusion behavioral symptoms, paranoia, delusional misinterpretation & hallucination.

40. Can lead to - self injurious behavior, decreased self management, caregiver management problemsSynonyms of PTD: acute confusional state, intensive care unit (ICU) psychosis, post-traumatic psychosis, metabolic encephalopathy, organic brain syndrome, sundowning, toxic encephalopathy 28

41. Clinical feature contd… Posttraumatic headache Walker and co-authors found that nearly 38% of patients with moderate or severe TBI had acute posttraumatic headache, usually daily and most commonly in the frontal region.Almost all of the patients who reported posttraumatic headache at 6 months also reported symptoms at 12 months 29

43. Associated with PTA lasting >24 hours.

44. Focal cognitive deficits- amnesia, slowing ,apathy, affective lability, executive difficulties.

45. Catastrophic reactions, emotional incontinence might occur.

46. If symptoms are severe it is particularly important to rule out NPH, SDH. Coexisting DAT.30

48. Memory dysfunction.

49. Executive dysfunction.

50. Relatively preserved visuospatial, praxis & primary linguistic function.

51. May be severely apathetic & withdrawn , slow information processing.

52. TBI is associated with Alzheimer’s disease.

53. TBI is associated with expression of amyloid precursor protein, oxidative stress & deposition of amyloid beta peptide that lead to the onset of dementia.

54. Chronic subdural hematoma in elderly can lead to progressive dementia.31

56. Associated injury to orbitofrontal lobe or anterior temporal lobe.

57. Frontal lobe syndrome is characterized by disinhibition, impulsivity, irritability, aggressive outburst.

58. Pseudo- depressed personality syndrome: apathy, blunted affect.

59. Pseudo -psychopathic personality syndrome: disinhibition, egocentricity & sexual inappropriateness.32

61. One Year Cumulative Incidence of Mood Disorders After TBI Jorge et al., 2004 34

62. Rates of Major Depression after TBI(N=559) Bombardier, Fann et al, unpublished Percent of cases (N=559) Cumulative incidence (53%) Prevalence Incidence Months after traumatic brain injury

63. Impact of Depression on Outcomes Depression after TBI contributes to: increased aggressive behavior and anxiety (Tateno et al., 2003; Jorge et al., 2004; Fann et al., 1995) significantly higher rates of suicidal plans (Kishi et al., 2001) 8 times more attempts (Silver et al., 2001) 3-4 times more completed suicide than in the general population and non-brain injured controls (Teasdale and Engberg, 2001) 36

64. Impact of Depression on Outcomes Depression after TBI contributes to: Poorer cognitive functioning (Rappoport et al., 2005) Lower health status and greater functional disability (Christensen et al., 1994; Levin et al 2001; Fann et al., 1995; Hibbard et al., 2004; Rapoport et al., 2003) Poorer recovery (Mooney et al., 2005) More post-concussive symptoms (Fann et al., 1995; Rapoport et al., 2005) 37

68. Pathologic laughing and crying

69. Rage and aggression

70. Altered sexual behavior

71. Lack of concern over consequences of actions

72. Social indifference

73. Inappropriate joking and punning

74. Superficiality of emotions40

76. Immediate or latent onset

77. Symptoms may resemble schizophrenia: prevalence 0.7% *

78. Schizophrenics have increased risk of TBI.

79. Patients developing schizophrenic-like psychosis over 15-20 years is 0.7-9.8%

80. May have epileptiform activity and temporal lobe lesions* van Reekum et al. J Neuropsychiatry ClinNeurosci 2000;12:316-327 41

82. Posttraumatic seizures: It frequently occur after moderate or severe TBI. The incidence of late PTS is in the range of 5-18.9%. Seizures are usually general or partial, and absence seizures are uncommon Immediate seizures < 24 hours. Early seizures 2-7 days, and late seizures - after 7 days. 43

83. Punch-drunk syndrome: Boxers may develop diffuse injury to the cortex, basal ganglia. Extra pyramidal symptoms or a subcortical dementia. Pathology shows cerebral atrophy & neurofibrillary tangles. 44

84. Sequelae in children: Less psychopathology after TBI due to increased brain plasticity. Recovery may continue for up to 5 years after injury. Problems are generally behavioral in nature – aggression, delinquency, ADHD like syndrome. 45

85. TBI-associated Disability “Postconcussive Symptoms” Cognitive Physical: sensory and motor Emotional Vocational Social Family 46

86. Postconcussive Syndrome: Headache Dizziness Blurred Vision Bothered by Noise Bothered by Light Loss of Temper Easily Memory Difficulties Fatigue Trouble Concentrating Irritability Anxiety Sleep Disturbance 47

87. Number of Postconcussive Syndrome: * p=.05 All symptoms * Depressive symptoms excluded 48

88. Thursday, February 8, 2007 PRO FOOTBALL Expert Ties Ex-Player's Suicide To Brain Damage From Football Since the former National Football League player Andre Waters killed himself in November, an explanation for his suicide has remained a mystery. But after examining remains of Mr. Waters's brain, a neuropathologist in Pittsburgh is claiming that Mr. Waters had sustained brain damage from playing football and he says that led to his depression and ultimate death. 49

89. PROGNOSIS 50

90. Predictors: GCS score- - Mild: 13-15 - Moderate: 9-12 - Severe: 3-8 Loss of consciousness(LOC)- -Mild: LOC <30 min. - Moderate: LOC 30 min- 6 hrs - Severe: LOC >6 hrs. Galveston Orientation & Amnesia Test(GOAT) Duration of PTA 51

92. Increased duration of PTA

93. Increased duration of PTD

94. Increased age, arteriosclerosis

95. Increased area of damage

96. Increased neurological sequelae

97. Dominant or bilateral involvement.52

99. Emotional impact of injury

100. Iatrogenic factors

101. Home & social environment

102. Compensation & litigation issues

103. Post traumatic epilepsy- 5% in closed & 30% in open TBI

104. Size & location of brain damage: frontal, temporal, dominant side worse.53

105. Outcome: Death Persistent vegetative state Severe disability(conscious but dependent for daily activities) Moderate disability(disabled but living independently) Good recovery. 54

106. MANAGEMENT: ASSESMENT TREATEMENT 55

107. Neuropsychiatric History Psychiatric symptoms may not fit DSM-IV criteria Focus on functional impairment Document and rate symptoms Explore circumstances of trauma LOC, PTA, hospitalization, medical complications Subtle symptoms - may fail to associate with trauma How has life changed since TBI? Thorough review of medical and psychiatric records. Talk with family, friends, caregivers Assess level of care and supervision available Assess rehabilitation needs and progress 56

108. Laboratory investigations: Serum biochemistry Neuroimaging Electrophysiological studies 57

110. Glial proteins: Myelin basic protein, Syneptophysin-100B

113. MRI scan : Investigation of choice for non-hemorrhagic lesions.

114. Delayed MRI scan: Indicated after 2 weeks with persistent neurological deficit after a neurosurgical procedure if the previous CT scan is normal.

115. PET & SPECT : gives additional information regarding metabolic rates of cortical & subcortical structures.

116. Proton magnetic resonance spectroscopy(MRS): More accurate than conventional MRI

117. Diffuse tensor MRI: For Degree of diffuse axonal injury & white matter pathology59

119. Video EEG or 24 hr ambulatory EEG: for unclear paroxysmal behavioral disturbances.

120. Quantitative EEG(QEEG): for slow wave abnormalities following TBI & post traumatic temporal lobe epilepsy.

121. Polysomnography: for diagnosing atypical sleep disturbance occurring after TBI.

122. Auditory evoked potentials: In detecting brain stem pathology.60

123. GOLDEN RULE: START LOW, GO SLOW May still need maximum doses Therapeutic onset may be latent Medications may lower seizure threshold Medications may slow cognitive recovery Monitor and document outcomes 61

124. Neuropsychiatric Treatment: Use Biopsychosocial Model Treat maximum signs and symptoms with fewest possible medications TBI patients more sensitive to side effects 62

126. Treatment contd… Dementia: behavioural modification cognitive rehabilitation psychotropic medication for specific syndromes or symptoms Piracetam Donepezil family or network intervention social services medical support in legal proceedings. 64

127. Treatment contd… Depression / Apathy Selective serotonin re-uptake inhibitors (SSRIs) - sertraline - paroxetine - fluoxetine - citalopram - escitalopram venlafaxine, duloxetine (may help with pain) bupropion (may decrease seizure threshold) nefazedone (may be too sedating, liver toxicity) mirtazapine (may be too sedating) Tricyclics: nortriptyline, desipramine methylphenidate, dextroamphetamine Electroconvulsive Therapy – consider less frequent, nondominantunilateral Apathy: Dopaminergic agents - methylpyhenidate, pemoline, bupropion, amantadine, bromocriptine, modafinil 65

128. Treatment contd… Mania Acute Benzodiazepines Antipsychotics olanzapine, risperidone, clozapine, others Anticonvulsants valproate Electroconvulsive Therapy Chronic valproate carbamazepine lamotrigine lithium carbonate (neurotoxicity) gabapentin, topiramate (adjunctive treatments) 66

132. Behavioral & Psychotherapeutic treatment: Behavioral rehabilitation program- contingency contracts & token economy. CBT Group therapy Family therapy 70

133. Take home messages: Neuropsychiatric syndromes are common after TBI They can present in many different ways. They can significantly increase distress, disability, and health care utilization. Use biopsychosocial and multidisciplinary approach. Treat as many symptoms with as few medications as possible. Monitor systematically and longitudinally 71

135. www.medspace.com

136. www.braininjury.com

137. www.traumaticbraininjury.net

138. www.northeastcentre.com

139. www.googleimage.com72

140. 73 THANK YOU

141. Cognitive Impairment May accelerate recovery May impede recovery amphetamine haloperidol Norepinephrine (TCAs) phenothiazines gangliosides prazosin methylphenidate, dextroamphetamine clonidine amantadine phenoxybenzamine L-dopa/ carbidopa GABA bromocriptine benzodiazepines pergolide phenytoin physostigmine phenobarbital donepezil idazoxan selegiline apomorphine caffeine phenylpropanolamine Naltrexone atomoxetine 74