TBI Potpourri: Update 2011

Michael R. Yochelson, MDMichael R. Yochelson, MD

VP of Medical AffairsVP of Medical Affairs

Medical Director, Brain Injury ProgramsMedical Director, Brain Injury Programs

October 27, 2011October 27, 2011

NRH/ReMeD/BIADC Joint Conference An Overview of Brain Injury:

25 Years of Experience

Topics

• Sleep

• Fatigue

• Psychosis

• Neuro-endocrine dysfunction

• Sports related TBI

• Blast Injury (military)

• TBI vs PTSD

• The real potpourri

SLEEP

• Insomnia

• Circadian Rhythm Disorders– Delayed Sleep Phase (DSP)– Irregular Sleep Wake Cycle (ISWC)

• Sleep apnea– Obstructive– Central

• Narcolepsy

Circadian Rhythm Dysfunction

SLEEP

• 68% of mod-severe patients admitted to inpatient rehab unit

• Increased length of stay

• Impact on behavior

• Impact on cognition

• Impact on function

• Impact on headaches/pain

SLEEP

• Evaluation– Patient/caregiver survey– Observational logs– Actigraph

• Accelerometer which is worn on the wrist

SLEEP

• Treatment– OSA/CSA

• CPAP/BiPAP• Avoid TCA• Reduce/avoid opioids if possible (may cause

opioid induced sleep apnea)

– Circadian Rhythm Dysfunction• Light therapy (not studied in TBI)• Sleep consolidation

– Sleep Hygeine

SLEEP

• Treatment– Pharmacological

• Circadian Rhythm– Melatonin– Ramelteon (Rozerem), a melatonin analog

• Sleep initiation/maintenance– Zolpidem (Ambien), eszopiclone (Lunesta), zaleplon

(Sonata)– Benzodiazapines (e.g., Ativan, Valium) ???

SLEEP

• Treatment– Insomnia associated with depression

• Trazodone (Desyrel)• SSRIs • Tricyclic antidepressants (e.g. amytriptyline/Elavil;

nortriptyline/Pamelor)

– Insomnia associated with agitation/ psychosis• Newer generation antipsychotics: quetiapine

(Seroquel), ziprasidone (Geodon), olanzapine (Zyprexa), risperidone (Risperdal)

FATIGUE

• Secondary to sleep dysfunction

• Independent of sleep dysfunction

• Evaluate for sleep problems and treat if indicated

FATIGUE

• Physical fatigue

• Mental fatigue

• Frequent or long naps

FATIGUE

• Neuro-stimulants– Methylphenidate (Ritalin, Concerta)– Dextroamphetamine (Dexedrine)

• Modafinil (Provigil)– Jha, Weintraub et al. 2008 study showed no improvement in

fatigue in 53 patients with mod-severe TBI (required inpatient rehab) who are at least 1 year post-TBI

– Kaiser, Valco, et al. 2010 study showed no improvement in fatigue 20 patients, but DID show improvement in EDS

• Activating antidepressants– Sertraline (Zoloft)

• Other antidepressants

PSYCHOSIS

• Acquired Brain Injury Related Psychosis (ABIRP)– Incidence: 0.7-9%– Hallucinations– Delusions– Lacks negative symptoms (e.g. catatonia)

PSYCHOSIS

• Risk Factors– Male– Premorbid neurodevelopmental hx– Premorbid psychiatric d/o– Substance abuse– Family h/o schizophrenia– Severity: severe>moderate>mild– Abnormal CT/MRI– Abnormal EEG/epilepsy– Cognitive impairment– Other psych d/o

PSYCHOSIS

• Evaluation– Infectious – Metabolic– Hydrocephalus/shunt malfunction– Medication side effects– Seizures

PSYCHOSIS

• Treatment of ABIRP– Atypical antipsychotics

• Quetiapine• Risperidone• Olanzapine (avail oral disolving tablet “Zydis”)• Ziprasidone (avail IM)

– Other options?• Haloperidol• Clozaril• Benzodiazepines

NEURO-ENDOCRINE

• Dysfunction– 5-20% of TBI patients will have some neuro-

endocrinological dysfunction– 25% decreased growth hormone– 50% (severe TBI) decreased AM cortisol– Other common dysfunction: hypo- or

hyperthyroidism, decreased testosterone, increased prolactin

– Increased prolactin decreased dopamine

NEURO-ENDOCRINE

• Subjective cold sensation (normal TSH)– Treat with DDAVP intranasal spray x 1-2

months

• Acne– Treat with minocycline

SPORTS

• Concussion: Features of concussion frequently observed – Vacant stare (befuddled facial expression) – Delayed verbal and motor responses (slow to answer questions or

follow instructions) – Confusion and inability to focus attention (easily distracted and unable

to follow through with normal activities) – Disorientation (walking in the wrong direction, unaware of time, date.

and place) – Slurred or incoherent speech (making disjointed or incomprehensible

statements) – Gross observable incoordination (stumbling, inability to walk

tandem/straight line) – Emotions out of proportion to circumstances (distraught, crying for no

apparent reason) – Memory deficits (exhibited by the athlete repeatedly asking the same

question that has already been answered, or inability to memorize and recall 3 of 3 words or 3 of 3 objects in 5 minutes)

– Any period of loss of consciousness (paralytic coma, unresponsiveness to arousal)

SPORTS:Symptoms of Concussion

• Early (minutes and hours) – Headache – Dizziness or vertigo – Lack of awareness of

surroundings – Nausea or vomiting

• Late (days to weeks): – Persistent low grade

headache – Light-headedness – Poor attention and

concentration – Memory dysfunction – Easy fatigability – Irritability and low frustration

tolerance – Intolerance of bright lights or

difficulty focusing vision – Intolerance of loud noises,

sometimes ringing in the ears – Anxiety and/or depressed

mood – Sleep disturbance

SPORTS: When to return to play

• Graduated Return to Play Protocol (Zurich, 2008)

Rehab Stage Functional Exercise Objective

No activity Complete physical & cognitive rest. Recovery

Light Aerobic Walk, stationary bike, swim. <70% max pred HR. No resistance exercise.

Increase HR

Sport specific exercise Skating drill (ice hockey), running drills (soccer). No head impact activities.

Add movement

Non-contact training drills

More complex training drills (e.g., passing drills). May begin progressive resistance training.

Exercise, coordination, cognitive load

Full contact practice AFTER medical clearance, participate in normal training activities.

Restore confidence; assessment of functional skills by coaching staff

Return to play Normal game play.

BLAST INJURY

• PRIMARY INJURY– Pressure wave transmitted through calvarium

• SECONDARY INJURY– Blunt or penetrating trauma

• Flying debris

• QUATERNARY INJURY– Victim thrown

• QUATERNARY INJURY– Gas, chemicals, etc. from explosion

• QUINARY INJURY– Hyperinflammatory state– Biologics

Brain injury in…Vietnam War: 12-14%

Persian Gulf War: 8%

OIF/OND/OEF*: 22%

*OIF = Operation Iraqi Freedom OND = Operation New Dawn OEF = Operation Enduring Freedom

• US Statistics:– Iraq (OIF)

March 19, 2003-August 31, 2010

• Fatalities: 4,421 U.S. Troops• Wounded: 31,921 U.S. Troops

– Afghanistan (OEF) Oct 2001-Sept 2011

• Fatalities: 1,749 U.S. Troops• Wounded: 13,609

• Approximately 8% of US Troops leave theater with a diagnosis of TBI.

• UK Statistics:– Iraq (Op TELIC)

January 1, 2003-July 31, 2009• Fatalities: 179 UK Military &

Civilian• Wounded: 537 UK Military &

Civilian– Afghanistan (Op HERRICK)

October 1, 2001-September 15, 2011 • Fatalities: 381 UK Military &

Civilian• Wounded: 2,326 UK Military &

Civilian

US & UK CASUALTIES IN IRAQ & AFGHANISTAN

http://www.defense.gov/news/casualty.pdfAccessed on September 6, 2011

http://www.mod.uk/DefenceInternet/FactSheets/Accessed on October 2, 2011

BLAST RELATED TBI: Incidence

• Approximately 20% of all deployments• Approximately 28% of all service members medically

evacuated out of Iraq/ Afghanistan• Approximately 88% of all service members medically

evacuated to WRAMC• Up to 97% of injuries are blast related (data from 1 unit)

– 53% involved head & neck

• The number of Iraqi and Afghan civilian casualties is even greater.

• Increasing number of civilian blast injuries worldwide.

TBI vs PTSD

• TBI– Cognitive dysfunction– Physical impairment

• Weakness, imbalance

– Dizziness– Headache– Depression/anxiety– Personality/behavioral

changes– Sleep dysfunction– Fatigue– Impulsive

• PTSD– Cognitive dysfunction– Dizziness– Sleep dysfunction– Fatigue– Depression– Anxiety– Nightmares– Hypervigilant– Startles easily

TBI vs PTSD

• TBI– Neuropsychology

• Neuropsych Testing• Cognitive remediation/

psychotherapy

– SLP• Speech, Language &

Cognitive skills

– PT/OT• Improve function,

edurance

– Medications• Headaches, depression,

fatigue, sleep disturbance

• PTSD– Psychology

• Psychotherapy

– Medications• Anxiety• Depression• Pain• Hallucinations• Fatigue• Sleep disturbance

TBI vs PTSD

• Can you get PTSD after TBI?– After mild?– After severe?– After blast?

• How can you differentiate TBI from PTSD?

• Is there a need to differentiate TBI from PTSD?

• Are there markers?

The real potpourri

• Omega-3 Fatty Acid Docosahexaenoic Acid (DHA)– Animal studies– Taking DHA prior to TBI appears to be

protective

The real potpourri

• Hypothermia – Therapeutic vs. non-therapeutic hypothermia– Preliminary data suggests that therapeutic

hypothermia is beneficial.– Retrospective study of non-therapeutic

hypothermia in severe TBI.• 10% incidence of SICU severe TBI population• Significant increase in mortality (OR 2.9)

The real potpourri

• Long-term Consequences of TBI– Causal relationship

• Penetrating TBI premature mortality• Severe or moderate TBI unprovoked seizures

The real potpourri

• Long-term Consequences of TBI– Association

• Penetrating TBI decline in neurocognitive function• Penetrating TBI long-term unemployment• Severe TBI neurocognitive deficits• Mod-Sev TBI Alzheimer’s dementia• Mod-Sev TBI Parkinsonism• Mod-Sev TBI Endocrine dysfunction (esp.

hypopituitarism)• Mod-Sev TBI growth hormone insufficiency

The real potpourri

• Long-term Consequences of TBI– Association

• Mod-Sev TBI Long-term adverse social-function outcomes (esp. unemployment, relationships)

• TBI Depression• TBI Aggressive behaviors• TBI Postconcussion symptoms• Professional boxing dementia pugilistica

The real potpourri

• Miscellaneous neuroprotection– Citicoline

• Improve memory & behavior• NIH study: Citicoline for the Treatment of TBI

– Progesterone• Decrease cerebral edema, increase BBB protection,

limits cellular necrosis & apoptosis• Decrease mortality (30 vs 13% in phase II trial)• Phase III trial: Study of the Neuroprotective Activity of

Progesteroen in Severe TBI (SyNAPSe)

The real potpourri

• Miscellaneous neuroprotection– Cyclosporine

• Improve CPP & cerebral metabolism• Phase II trials only; limited data

– Decompressive craniectomy• 2 phase III trials enrolling

– Surgery vs. medical management

The real potpourri

The real potpourri

CONCLUSIONS

• Sleep dysfunction is a significant problem for patients with TBI and should be evaluated and treated appropriately.

• Fatigue may be related to sleep dysfunction or independent.

• Psychosis is not that common, but can be severely impairing and can lead to severe psychosocial problems.

• Know your grading and guidelines for sports concussion/TBI.

• Blast injury – what’s the impact? • Much research needed in differentiating TBI from PTSD

QUESTIONS?