traumatic brain injury and pain f.antonio luque, m.d. ph.d. neurology
TRANSCRIPT
Traumatic Brain Injury and Pain
F.Antonio Luque, M.D. Ph.D.
Neurology
Traumatic Brain Injury
TBI in the USA estimated 180-200 cases/100,000
Around 600,000 New TBI occur every year
10% of these Injuries are fatal.
NIH survey estimates in USA 1.9 million suffer skull fracture or intracranial injury, ½ have suboptimal outcome.
Cost 40 Billion dollars/year
TRAUMATIC BRAIN INJURY
Military Fatalities: By Time PeriodAs of 2/20/07
Period US UK Other* Total Avg Days
5 998 34 21 1,053 2.43 434
4 715 13 18 746 2.35 318
3 579 25 27 631 2.92 216
2 718 27 58 803 1.89 424
1 140 33 0 173 4.02 43
Total 3,150 132 124 3,406 2.37 1,435
US Non Mortal Casualties: Including non-hostile and medical evacuations
As of 2/3/07
Non-Mortal Casualities
Army
Navy
Marines
Air Force
Total
Wounded – No Medical Air Transport Required
10,120 385 5,698
209 16,412
Wounded – Medical Air Transport Required
5,009 137
1,804
55 7,005
Non-Hostile Injuries – Medical Air Transport Required
5,439
223 895
278 6,835
Disease – Medical Air Transport Required
16,111
544
1,209
840 18,704
TOTAL – WOUNDED 15,129 522 7,502 264 23,417
TOTAL – MEDICAL AIR TRANSPORTED
26,559
904
3,908
1,173 32,544
Traumatic Brain InjuryTraumatic brain injury symptoms
Inability to find words
Inability to perform tasks
Confabulating (putting unrelated bits of conversation into conversation gaps)
Impulsivity
Agitation
Poor judgment and poor insight
Sexual inappropriateness, including a lack of sexual inhibitions
For more information, call (800) 877-VETS, or visit www.va.gov.
Frequency of PCS Symptoms following a MTBI
• Poor concentration 71%• Irritability 66%• Tired a lot more 64%• Depression 63%• Memory problems 59%• Headaches 59%• Anxiety 58%• Trouble thinking 57%• Dizziness 52%• Blurry or double vision 45%• Sensitivity to bright light 40%
Traumatic Brain Injury, VA Health Initiative
Causes of TBI (CDC Data)
• Transportation (MVA) 48.9%
• Falls 25.8%
• Firearms 9.7%
• Other Assaults 7.5%
• Others 7.4 %
• Unknown 0.6%
Traumatic Brain Injury, VA Health Initiative
Severity Grades of TBI
• Mild (Grade 1 ): altered or LOC <30 min with normal CT or MRI, GCS 13-15, PTA < 24 hours.
• Moderate (Grade 2): LOC < 6 hours with abnormal CT and/or MRI, GCS 9-12, PTA < 7 days.
• Severe (Grade 3 & 4): LOC > 6 hours with abnormal CT and/or MRI, GCS < 9, PTA > 7 days.
Traumatic Brain Injury VA Health Initiative
Functional Correlates of Injury Pathophysiology
• Focal Cortical Contusion: ground level fall, assault, gunshot wound. They can have Hemiparesis, aphasia, Seizures, visuoperceptual.
• Diffuse Axonal Injury: motor vehicle accident, non-ground level fall, geriatric ground level fall. They have confuse language, amnesia, apraxia, hypoarousal.
• Hypoxic/Ischemic: anoxia, cardiac arrest, prolonged elevated ICP. They have quadriparesis, spasticity, confusion, amnesia, hypoaraousal.
Traumatic Brain Injury VA Health Initiative
Frequency of PCS Symptoms following a MTBI
• Poor concentration 71%• Irritability 66%• Tired a lot more 64%• Depression 63%• Memory problems 59%• Headaches 59%• Anxiety 58%• Trouble thinking 57%• Dizziness 52%• Blurry or double vision 45%• Sensitivity to bright light 40%
Traumatic Brain Injury, VA Health Initiative
Specific or subjective PCS
• Neurological or medical: Headaches, Dizziness/vertigo, Tinnitus, blurred or double vision, light and or noise sensitivity, Nausea and vomiting, Fatigue, sleep disturbances, Physical weakness.
• Cognitive: Memory complaints, concentration complaints.
• Psychological: Irritability, Increase aggression, Depression, Anxiety.
Traumatic Brain Injury VA Health Initiative
Referrals ( Team work)• Audiologist• Kinesiotherapist• Neuro-ophthalmologist• Occupational therapist• Recreational therapist• Speech and language pathologist• Case manager• Neurologist• Neuropsychologist (psychologist)• Physiatrist• Psychiatrist• Social worker (counselor)• Vocational rehabilitation counselor
Traumatic Brain Injury VA Health Initiative
Comprehensive Assessment of Acquired Brain Injury
History: Accident related facts
Initial neurological presentation
Pre injury information
past medical history and surgical history substance abuse
developmental history
educational history.
Military and legal records
Vocational History
Psychological history
Life stressors
Family history
Post injury treatment interventions
Current functional status
Physical Examination:
Neurological
Cranial nerves 1-12
Deep tendon reflexes and pathological
Sensory exam
Cerebellar exam
Motor exam
Mental status exam
Behavioral assessment
Emotional/psychological status
Musculoskeletal
Head
Face and temporomandibular joints
Extremities
Axial structures (neck, back, pelvis)
Traumatic Brain Injury VA Health Initiative
Chronic cognitive problems
• Attention problems
• New learning and memory problems
• Executive control dysfunction
• Others (orientation, communication, behavioral, bradyphrenia, etc)
Traumatic Brain Injury VA Health Initiative
Interplay of cognitive and emotional problems
Psychogenic/Psychiatry symptoms Denial
Anger and irritability
Depression
Rigid compulsive/hypervigilant
Emotional lability
Social withdrawl
Sense of futurelessness
Thought disorder
Personality and conduct disorder
Neurogenic symptoms Anasognosia (lack of awareness of
impairment)
Frustration, catastrophic reaction, reduce information
Lack of initiative, impaired emotional expressiveness (Aprosodias), lower
crying threshold, fatigue
Distractability, inabilityto deal with more than one task at a time, dependence on external controls.
Lability of emotional expressiveness (not the underlying feeling state)
Lack of initiative
Impaired planning
Aphasia, anomia, or confusion
Impulsivity, social disinhibition
Traumatic Brain Injury VA Health Initiative
• Acute Pain:”Normal sensation triggered by the nervous system to alert you to possible injury.”
• Chronic Pain:”Pain persists, signals keep firing in the nervous system for weeks, months, even years”
NINDS Chronic Pain information page
Pain
• Tissue injury trigers an inflammatory cascade that will alter nociceptive function.
• Plasticity and learning play a role in pain• Synaptic potentiation is facilitated by repetitive noxious
stimulation and at the level of the brain,environmental influences alter the response to noxious stimulation.
• The brain can generate pain in the absence of input from the peripheral nociceptors or the spinal cord. e.g. phantom limb pain
• Therefore a Brain pattern generating mechanism or Neuromatrix has been proposed
Pain: an overview, JD Loeser, R.Melzack . The Lancet 1999: 1607-1609
International association for the Study of Pain:
“Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or describe in terms of such damage”
JD Loeser, R Melzack, The Lancet 1999: 1607-1609 (Pain: an overview)
Components of Pain• Nociception: detection of tissue damage by specialized
transducers attached to A delta and C fibers. Aspirin can prevent inflammation and Local and regional anesthesia can prevent nociception.
• Perception of Pain: triggerd by noxious stimulus, It can be generated by lesion in the peripheral or central nervous system.e.g. diabetic neuropathy, spinal cord injury or stroke. Pain can occur without nociception. The intensity of chronic pain has no relation to the extent of tissue injury or other pathology.
• Suffering:negative response induce by pain and by fear, anxiety, stress, loss of loved objects and othr psychological states. Cassell:”Suffering occurs when the physcial and psychological integrity of the person is threatened”.
• Pain Behaviors: results from pain and suffering and the things the person do or does not do. Examples:”ouch”, gramacing, limping, lying down , recourse to health care, refusing to work, etc.
JD Loeser, R. Melzack, The Lancet 1999: 1607-1609 (Pain: an overview)
The neurobiology of pain, Besson JM The Lancet,1999:353: 1610-1615
Histamine, serotonin, bradykinin, prostaglandins, ATP, H+ ,NGF, TNF alpha, endothelins, interleukins
Pain treatment options: TCA, anticonvulsants, Na+ channel blockers, NMDA receptor antagonists, opioids
Molecular Events of PainPeripheral
Transduction• TRPV1, TRPV2, TRPV3, TRPM8• ASCI, DRASIC• MDEG, TREK-1• BK1, BK2
• P2K3
Peripheral sensitization• NGF, TrkA• TRPV1• Na, 1,8• PKA, PKC isoforms, CalMK IV• Erk1/2, p38, JNK• IL-1β, cPLA2, COX2, EP1, EP3, EP4• TNFαMembrane excitability of primary afferents• Nav 1.8, Nav 1.9• K+ channelSynaptic transmission Presynaptic• VGCC• Adenosine-R• (mGlu-R)
J.Scholz, CJ Woolf:Can we conquer pain? , Nature Neuroscience 2002: 10621067
Molecular Events of PainCentral
Synaptic transmission Postsynaptic• AMPA/kainate-R, NMDA-R, mGlu-R• NK1• Nav 1.3• K+ channelsCentral inhibition• GABA, GABAA-R, GABAB-R• Glycine-R• NE, 5-HT• Opioid receptors• CB1Signal transduction• PKA, PC isoforms• ERK, p38, JNKGene expression• C-fos, c-jun, CREB• DREAM
J.Scholz, CJ Woolf: Can we conquer pain? Nature Neuroscience 2002: 1062-1067
The National Initiative on Pain Control, 2002
The National Initiative on Pain Control, 2002
The National Initiative on Pain Control, 2002
The National Initiative on Pain Control, 2002
The National Initiative on Pain Control, 2002
The National Initiative on Pain Control, 2002
The National Initiative on Pain Control, 2002
The National Initiative on Pain Control, 2002
BRAIN IMAGING TECHNIQUESPET• Requires relatively long pain stimulation periods (40 – 60s).• Different functional states (e.g., pain and rest) are always acquired in separate scans.• Maximum number of scans that can be acquired is limited by radioactivity dose restraints.• Usually requires multi-patient study designs.• Potential to map neurotransmitter systems and drug uptake in vivo and molecular imaging.• Provides a solution in cases where fMRI cannot be accomplished because of
contraindications.
fMRI• Offers better temporal and spatial resolution than PET.• Pain stimuli do not need to be applied over along period.• The control state and the active pain condition are done in the same run.• Better suited than PET for studying cognitive effects on pain processing.• Unlimited amount of repetitions within a single patient, allowing single participant, and follow-
up studies.• Offers less comfort to the patient (noise, body constrained in the magnet bone).• Requires expensive fMRI-compatible stimulation and monitoring equipment.
MEG• Allows mapping of the sequential activation of brain structures in pain processing.• Provides a direct measure of neuronal activity.• The most ecological technique with the highest comfort and least distress for participants.• Allows conclusions from single trial and single participant studies (great clinical potential).Brain Imaging of clinical pain states..Kipers R, Kehlet H. The Lancet Neurology 2006: 5:1033-1044
Kupers R, Kehlet H The Lancet Neurology 2006: 1033-1044
Temporal SpatialResolution Resolution Advantages Disadvantages
_______________________________________________________________________
PET >49’s >4 mm Measures activity and Radioactivity. subcortical structures. Poor temporal resolution.Stimulus-independent Invasive technique.technique Limited amount of scansAllows receptor binding possible.studies
fMRI 100 ms – 3’s >2 mm Measures activity in Poor patient comfort.cortical and structures. Requires non-magneticExcellent spatial equipment.resolution. Stimulus-dependent
technique.
MEG Milliseconds >2 mm Excellent temporal Difficulties to measuresresolution. subcortical activity.High patient comfort. Requires non-magneticEcological method. equipment.
Stimulus-dependent technique.____________________________________________________________________________________
Characteristics of different brain imaging techniques used in the study of pain.
Kupers R, Kehlet H The Lancet Neurology 2006:1033-1044
Kupers R, Kehlet H, The Lancet Neurology 2006:1033-1044
METHODOLOGICAL DIFFICULTIES IN DESIGN OF BRAIN-IMAGING STUDIES IN CHRONONIC PAIN
• Difficulty in finding a homogeneous population of chronic-pain patients.
• Difficulty in discerning pain-related from psychological-related effects.
• Possible confound by differences in genetic constitution.• Difficulty in dissociation of deafferentiation-related from pain-related
changes in brain activation patterns.• Homologous contralateral area is not an unbiased site fro non-
painful control stimulation.• Difficulty in switching pain on and off in a very precise and time-
locked manner.• Effects of therapeutic interventions could be difficult to dissociate
from pain-related effects.Kupers R, Kehlet H.The Lancet Neurology 2006:1033-1044
B.R. Buchbinder, Division of Neuroradiology MGH, Boston, MA
B.R.Buchbinder, Division of Neuroradiology MGH, Boston, MA
Emergency Neuroradiology, M.Rothman et al. e-medicine, Oct 29, 2003
Epidural Hematoma
Head Injury, Olson DA et al. e-Medicine Oct 2, 2006
Right subdural hematomaIntraparenchymal bleeding
Head Injury, Olson DA et al. e-Medicine Oct 2, 2006
Left frontal contusion Right linear contusion
Emergency Neuroradiology, M Rothman, e-medicine Oct 29, 2003
Bullet
Emergency Neuroradiology, M.Rothman, e-medicine Oct 29, 2003
Metallic rod