Psychiatric Disorders and Traumatic Brain Injury

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Slide 1 :

Psychiatric disorders in post-traumatic brain injury ??.??.????? ???????????? ??????????????????? ????????????? ????????????????????

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To present evidence-based medicine regarding psychiatric disorders following traumatic brain injury (TBI) To review evidence-based treatment for cognitive dysfunction in patients with post-TBI 23/11/53 NW 2 Objectives

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Mild traumatic brain injury (mTBI) Minor traumatic brain injury Post concussive syndrome, brain concussion Closed head injury etc Moderate to severe traumatic brain injury (mod-sTBI) 23/11/53 NW 3 Types of traumatic brain injury (TBI)

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Cognitive function Psychological and psychiatric consequences Disability General functioning Quality of life Care giver burden 23/11/53 NW 4 Why care..

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??? GK ???? 37 ?? ?????????????????? ????????????????????????????????????? 6 ????????? ???????????????????????????? ?????????????? 6 ??? ???????????? 1 ???? ??????? ‘dizziness, memory loss, anxiety, PTSD like symptoms, headache, irritability, depression, sleep disturbance’ ?? CT brain/MRI brain ???? ??????????? ‘mood swing’ ??????????????????????? ?????????? ????????????? ?????????????? ???????????????????????????? ???????? ?????????? ????? ‘flashback’ ????????????????????? ????????? 30 ???????????????????? ??????????? “?? (???????) ??????????” ??????????? MVA ‘head injury’ ??????? 5 ?????? ??????????????????????? ??? 1 ?????????????????????????? psychiatric diagnosis ??????????? ?????????? gr. 12 ????? Citalopram 20 mg/d (6 ?????), clonazepam, TWC ?????????? 23/11/53 NW 5 Case example

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23/11/53 NW 6

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Headache Dizziness Irritability Anxiety Nausea/vomiting Blurred vision, light sensitive Tinnitus Insomnia Easy fatigability Impaired concentration Impaired memory 23/11/53 NW 7 Symptoms of mTBI

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23/11/53 NW 8

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44.3% prevalence of over 7.5 years Relative risk of 7.5 The data regarding a biologic gradient are mixed Premorbid psychiatric disorder and social impairments may contribute to post-TBI depression Depression not related to severity of TBI associated with neuropsychological impairment van Reekum et al 2000 23/11/53 NW 9 Depression

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Location of affected brain Rt. Hemisphere damage Lt. Dorsolateral frontal (MDD) Left basal ganglia (MDD) MDD Not a psychological response Less severe TBI Impaired social functioning seems to play a role van Reekum et al 2000 23/11/53 NW 10

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23/11/53 NW 11 Common sites of TBI

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23/11/53 NW 12 Common site of injury; serotonergic pathway

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23/11/53 NW 13 Common site of injury; noradrenergic pathway

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Younger age Poorer TBI outcome (GCS) Pre-TBI alcohol and psychiatric histories Lower MMSE Lower number of years of education van Reekum et al 2000 23/11/53 NW 14 Other characteristics

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Male 4.2% prevalence of over 7.5 years Relative risk of 5.3 Location Right hemisphere Limbic system Seizures Patients may have family history of mood disorder Not associated with severity of TBI, degree of physical or cognitive impairment, level of social functioning, or personal or family history of psychiatric disorder van Reekum et al 2000 23/11/53 NW 15 Bipolar disorder

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Generalized anxiety disorder 10% prevalence of over 7.5 years after TBI Controversy for biologic gradient Obsessive-compulsive disorder 6.4% prevalence of 7.5 years after TBI Relative risk of 2.6 Frontal system impairment is proposed Panic disorder 10% prevalence of 7.5 years after TBI Relative risk of 5.8 No available data to support pathophysiologic hypotheses van Reekum et al 2000 23/11/53 NW 16 Anxiety disorder

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Posttraumatic stress disorder Found in 82% of mTBI patients who had ASD, and 11% of those who did not Relative risk of 1.8 Rarely evidence for a temporal association given Not associated with a neurotic predisposition, but is strongly associated with horrific memories of the accident The ‘island of memory’ is preserved van Reekum et al 2000 23/11/53 NW 17

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0.7% prevalence of over 4.9 years of follow-up Relative risk of 0.5 van Reekum et al 2000 23/11/53 NW 18 Schizophrenia

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Substance abuse or dependence are common with prevalence of 22% Relative risk of 1.3 No available data to support pathophysiologic hypothesis van Reekum et al 2000 23/11/53 NW 19 Substance related disorder

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Avoidant, borderline, and narcissistic personality disorders are the most common Biologic gradient was mixed Temporal sequence was not assessed van Reekum et al 2000 23/11/53 NW 20 Personality disorders

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Subtypes Labile Disinhibited Aggressive Apathetic Paranoid Other Combined Unspecified 23/11/53 NW 21 Personality change due to..

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23/11/53 NW 22

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Diffuse axonal injury corpus callosum brain stem MRI studies Frontal temporal regions PET: hypometabolism Frontal Whole brain Hypoxia free radical excitotoxic neurotransmitter release 23/11/53 NW 23 Biological mechanisms

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23/11/53 NW 24

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Cholinergic dysfunction is main cause of cognitive deficits following mTBI temporal cingulate parietal Mice with multiple mTBI Aß and oxidative stress in the brain [Kunichiro 2002] Mimic Alzheimer’s disease Increased risk of dementia for carriers of the APOE e4 allele (A. Sundström et al 2007)

Slide 26 :

cholinergic dysfunction in the brain results in problems with attention learning storage retrieval behavioral change

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Increased DA is associated with memory deficits (in mice) 23/11/53 NW 27

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CSF Lower levels of substance P Lower levels of serotonin Higher lipid peroxidation products Increases 5-HT in extracellular fluid (in rats) Increases in GABA in the dentate gyrus Some changes of NTs systems may occur weeks after TBI 23/11/53 NW 28

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State of the problems Primary problem Cognitive consequences Psychiatric consequences Neurological testings, investigation Pharmacologic interventions Psychotropic drugs Symptomatic meds Cognitive enhancer Psychosocial interventions 23/11/53 NW 29 Management

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Treatment for cognitive symptoms Cholinergic agents Physostigmine improved memory and other cognitive deficits Physostigmine & lecithin improved verbal learning and memory CDP-choline improved visual recognition memory Eames P, et al 1995, Levin HS et al 1986, Walton RG. et al 1982, Weinberg RM et al 1987, McLean A Jr et al 1987, Cardenas DD et al 1994, Goldberg E et al 1982, Levin HS. et al 1991

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AChEI Small sample size and not a robust evidence Donepezil Taverni JP et al 1998: 3-wk trial, 2 pts with long term static memory dysfunction Whitlock JA et al 1999: 9 pts, 3 pts had increase at least 5 pnts on MMSE Masanic CA 2001: 12-wk, 4 pts improved memory Zhang L et al 2004: 24-wk, 18 pts improved short-term memory & sustained attention

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Rivastigmine With placebo 12 wks, 157 pts Improved memory on 81 pts with mod to severe TBI patients significantly Tenovuo O 111 pts with chronic TBI Suffered : fatigue, poor memory, diminished attention ???? diminished initiation Randomly assigned to donepezil, galantamine or rivastigmine subjective view Results: improved but not significantly different among another

Slide 33 :

Q&A 23/11/53 NW 33 Thank you !!

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