Surakrant Yutthakasemsunt , M.D Khonkaen Regional Hospital Khonkaen ,Thailand

1. Posttraumatic syndrome Surakrant Yutthakasemsunt , M.D Khonkaen Regional Hospital Khonkaen ,Thailand 23 June 2006

2. Consideration • Wastebasket term • No unique clinical diagnostic criteria • Controversy in etiological details • Inconsistency clinical presentation • Limit of study methodological problems

3. Related Terms • Posttraumatic syndrome:PTS • Posttraumatic stress disorder:PTSD • Posttraumatic stress syndrome • Posttraumatic neck syndrome • Post-Concussive Syndrome:PCS

4. Posttraumatic stress disorder Shell shock Battle fatigue Accident neurosis Post rape syndrome

5. Neurobiological Changes after TBI • cortical contusions (mostly in severe TBI) • results in a loss of function served by that area • white matter lesions • results in interruption of information processing between cortical areas • diffuse axonal injury • results in slowed and inefficient information processing • disproportionately affects glutamatergic and cholinergic projections • results in problems with attention, memory, and various aspects of frontally-mediated cognition (ie, working memory, executive function) • may affect serotonergic systems • dysfunction in these systems may secondarily affect the efficiency of function in dopaminergic or noradrenergic systems

6. Clinical Features • Somatic-organic or physical problems • Psychosocial or neuropsychiatry problems • Cognitive problems Mixed and fluctuating symptom features over time especially neuropsychiatry problems

7. Patterns of Post-Concussive Symptoms

8. Filter Effects of CNS Injury • What does depression look like in someone who is non-verbal? • What does manic hyperactivity look like in someone with quadriplegia? • How do hallucinations and delusions present in someone who cannot describe them?

9. Vulnerability to Side Effects • Neuropsychiatric patients show increased frequency & severity of side effects to most psychotropics • Can manifest as worsening of neurological problems (tremor, cognition, slowing, etc.)

10. Medications and Drugs Associated with Aggression • Alcohol: intoxication and withdrawal • Hypnotic and anxiolytics: intoxication and withdrawal • Analgesics (narcotics): intoxication and withdrawal • Steroids (prednisone, cortisone, and anabolic steroids) • Antidepressants: especially during initial phases of Rx • Amphetamines and cocaine • Antipsychotics: secondary to akathisia • Anticholinergic drugs: delirium • Quinolone antibiotics?

11. General Principles • Drug Impact on Cognition • Memory – Benzodiazepines, antidepressants (anticholinergic effects) • Attention – Benzodiazepines, neuroleptics • Speed of Information Processing – Benzodiazepines, neuroleptics, others • Thus the very areas most affected by TBI can be made worse!

12. Neurotransmitter Dysfunction after TBI • Many neurotransmitters are involved in the regulation of cognition, emotion, behavior, and physical/motor function • Principal neurotransmitters in regulation of frontal and frontotemporal functions include: • dopamine • norepinephrine • serotonin • acetylcholine • glutamate • gamma-aminobutyric acid (GABA)

13. Ways of Altering Synaptic Content of Neurotransmitters Synthesis Storage Release Binding Re-uptake Metabolism

14. Dopamine Agonists • A variety of agonists have been shown effective in animal models and are used clinically: • Methylphenidate (and other stimulants) • Amantadine • Bromocriptine • Bupropion

15. Alpha-2-Adrenergic Agonists • Infusion of A2A agonists improves WM function in primates and rodents • guanfacine can improve WM in healthy individuals and may improve working memory after TBI • Methylphenidate also has A2A agonist properties

16. Cholinergic Augmentation • Multiple studies demonstrate that cholinergic augmentation, generally using one of several cholinesterase inhibitors (e.g., physostigmine, donepezil) can improve TBI-induced attention and memory deficits even in the late post-injury period (>1 year) in some TBI survivors • Taverni 1998; Whelan 2000; Cardenas 1994; Arciniegas 2001

17. Prior to Treatment • Accurate diagnosis is critical first step • Know what you are treating before treatment • Are you treating the underlying disorder, or the comorbid psychopathology?

18. Neuropsychological Battery (Some) • Orientation • Galvestone Orientation and Amnesia Test (GOAT) • Motor • Grooved Pegboard test • Attention,Cognition processing Speed • Wechsler Memory Scale-Revised Digit Span • Symbol Digit Modality Test • Visual Scanning,Analysis and Construction • Trailmaking Test • Boston Visual Discrimination Test • Wechsler Adult Intelligence Scale-Revised Block Design (WAIS-RBD) • Language • Control Oral Word Association Test (COWAT) • Multilingual Aphasia Examination Token Test • Memory • Wechsler Memory Scale-Revised Logical Memory • Rey Auditory Verbal Learning Test (RAVLT) • Problem Solving • Wisconsin Card Sorting Test

19. Why learn about medications? • Improves care • Improves your clinical skills • Fosters participation in treatment • Facilitates holistic approach to care

20. Psychopharmacological Approach • Clarify/simplify current regimen • Clarify critical target symptoms to treat • Target specific symptoms

21. Medication approaches • amelioration of specific somatic symptoms (e.g., headache, dizziness, sleep disturbances) • amelioration of psychobehavior complications • augmentation of cognition

22. Dosage Considerations Start lower Go slower Stop sooner

23. Psychopharmacological Issues • At present, there are no FDA approved treatments for cognitive, emotional, or behavioral impairment due to TBI • Pharmacotherapies are generally modeled after those for patients with phenomenologically similar but etiologically distinct disorders (attention-deficit hyperactivity disorder, Alzheimer’s disease, etc.)

24. Physical Symptoms After Concussion • Headache • Fatigue • Dizziness/ Dysequilibrium • Insomnia • Aesthenia/ Weakness • Anosmia • Numbness/ Paresthesias • Photophobia • Tinnitus/ Hearing ↓↓ • Blurred Vision • Hypersensitivity to sound

25. Post-concussive Headache • Musculoskeletal –Myofascial – Upper Cervical Spine • Neurogenic – Greater or Lesser Occipital Neuralgia – Scalp Neuroma from laceration or contusion • Vascular – Not very common (although more-so in kids/predisposition) --Overlap in receptive fields for upper cervical dorsal horns and spinal tract of trigeminal nerve • “Dysautonomic”

26. Treatment of Post-Concussive Headache • Musculoskeletal: NSAIDs, Amitryptiline, TP injection, PT, Manual Medicine • Neurogenic: Injection, anticonvulsants, Amitryptiline, counter-stimulants, PT, TENS, Lidoderm patches • Vascular: Abortive Rx, Preventative Rx

27. Post-Concussive “Dizziness” Postural Instability vs Vestibular Dysfunction (vertigo, nystagmus)

28. Post-Concussive Postural Instability • Musculoskeletal • Neurological – Visual – Proprioceptive – Vestibular – Integrative

29. Post-Concussive Vestibular Dysfunction • Vertigo • Gaze Instability • Postural Control

30. Post-concussive Vestibular Problems • Benign Paroxysmal Positional Vertigo (habituates) • Central Positional (will not habituate) • Cervicogenic (habituates) • Perilymphatic fistula (bed rest, surgery) • Endolymphatic hydrops – Betahistine, suppressants, surgery • Unilateral Vestibular Loss • Bilateral Vestibular loss – head and neck are rigid, gaze unstable

31. Evaluation of Post-Concussive Dizziness • Neuro-otology consult • Imaging • Electronystagmography (ENG) • Caloric/rotary testing • Posturography

32. Treatment of Post-concussive Dizziness • Physical Therapy – Habituation Exercises – “Liberatory” Exercises (BPPV) – Oculo-vestibular Exercises • Behavioral • Pharmacological • Surgery

33. Pharmacological Treatment of Post-Concussive Dizziness • Meclizine (Antivert) • Scopolamine (anticholinergics) • Benzodiazepines • Antihistamines – Loratadine ? All may impede “natural” recovery and/or effectiveness of therapy

34. Emotional/Affective Symptoms After Concussion • Irritability • Lability /inappropriate emotions (Mood change) • Depression • Anxiety/agitation • Decreased libido • Impulsive

35. Despite Diagnostic Challenges • When behaviors change: • New behaviors • Change in frequency and intensity of previous behaviors • Have a high index of suspicion for the common psychiatric disorders

36. Common Behavioral Syndromes in the Injured Brain • Depressive Syndromes • Dyscontrol Syndromes • Attention Deficit Syndromes • Sleep Disorders • Psychotic Syndromes

37. Psychiatric Disorders and TBI • Disorders of thought content and thought process complicate recovery from TBI • Psychotic syndromes occur at rates greater than those in general population • Injury severity positively correlated with risk • Even in absence of formal criteria,many with TBI have psychotic symptoms

38. Other Links to Psychosis • PTA • resembles delirium in many respects • Restlessness, fluctuating level of consciousness, agitation. • Hallucinations and delusions occur frequently • Mood Disorders • Depression • Mania • Seizure Disorders

39. Aggression and TBI • Acute phase: 35% - 96% of patients exhibit agitated behaviors • 89 patients assessed during the first six months after TBI, aggressive behavior found in 33.7% of TBI patients, compared to 11.5% of patients with multiple trauma but without TBI (Tateno et al) • Recovery phase: 31% - 71% of patients with severe TBI and 5% - 70% of patients with mild TBI are agitated or irritable • Irritability increases with more TBI’s

40. Characteristics of Aggression After TBI • Reactive: Triggered by modest or trivial stimuli • Nonreflective: Usually does not involve premeditation or planning • Nonpurposeful: Aggression serves no obvious long-term aims or goals • Explosive: Buildup is NOT gradual • Periodic: Brief outbursts of rage and aggression, punctuated by long periods of relative calm • Ego-dystonic: After outbursts, patients are upset, concerned, and/or embarrassed, as opposed to blaming others or justifying behavior

41. Neuropathology of Aggression • Hypothalamus Orchestrates neuroendocrine response to sympathetic arousal Monitors internal status • Limbic system Amygdala Activates and/or suppresses hypothalamus Input from neocortex Temporal cortex Associated with aggression on both ictal and interictal status • Frontal neocortex Modulates limbic and hypothalamic activity Associated with social and judgment aspects of aggression

42. Factors Associated with Agitation in Brain Injury Medical Illness Aggression as direct effect of Brain Injury Adverse Environment Psychosis Depression AGITATION Sundowning Anxiety Insomnia

43. “Past” Treatment of Agitation • Agitation often treated non-specifically with sedatives • Should target underlying causes • No medication is approved by the FDA for agitation or aggression • May reflect inconsistent concepts and goals

44. Approach to Dyscontrol Syndromes • Consider if due to: • Depression • Mania • Psychosis • Environmental factors • Anxiety • If so, treat accordingly

45. Evaluation of Cognitive and Emotional Symptoms • Imaging (not usually very helpful) • Neuropsychological Assessment • Detailed past history • Differential etiologies – Medications – Concurrent illness – Sleep disorders

46. Treatment of Post-Concussive Affective/Emotional Problems • Correct sleep disturbances • Counseling Pharmacological – SSRI’s – Anticonvulsants (valproate, carbamazepine) – Propranolol – Psychostimulants – Atypical antipsychotics ?

47. Approach to Depression • Trials of • SSRI • second SSRI • Low dose Desipramine or Bupropion • Other • MAOIs • ECT

48. Approach to Mania • Valproic Acid • Lithium • Combination approaches • Newer anticonvulsants • Lamotrigine • Topirimate

49. Approach to Dyscontrol • If not due to other conditions: • Beta blockers • Lithium • SSRI’s • Antipsychotics • Calcium channel blockers • Anticonvulsants

50. Nonpharmacological Approach • Modify environment • Optimize stimulation • Use consistent routines • Assess/adapt to aggravating factors • Behavior management principles • Education • Support of patient and caregivers