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Dr Mayur Bodani Consultant Neuropsychiatrist Raphael Medical Centre 26.11.14
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Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Aug 01, 2018

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Page 1: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Dr Mayur Bodani

Consultant Neuropsychiatrist

Raphael Medical Centre 26.11.14

Page 2: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Epidemiology traumatic brain injury (tbi)

Definitions

Sleep disorders in tbi

Disorders of fatigue in tbi

Possible pathophysiology

Page 3: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Neil Munroe

• Brain Maps

Page 4: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

‘damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia, skull fracture, or objective neurological findings that can be reasonably attributed to tbi on physical examination or mental status examination’

TBI Model Systems Task Force, 1998

Page 5: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Focal

Diffuse

Haemorrhagic

Non-haemorrhagic

Coup and contrecoup

Contusional

Compressive (epidural and subdural)

Page 6: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Natural traumatic forces never injure the brain in exactly the same way

Neural circuits will be differentially impaired

Different degrees of dysfunction from individual to individual

Further permutation of each brain’s own unique set of premorbid strengths and weaknesses

Page 7: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

1.6 million to 3 million tbi’s in the US and worldwide

51,0000 deaths pa

15,000-20,000 victims in France pa

5-10% severe tbi

Men> Women 2:1

Falls/RTA’s main cause

Young age group: 12-25

290,000 hospitalizations

Page 8: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Mild

13-15

Moderate

9-12

Severe

<= 8

Other Factors:

Mechanism

Open/closed

Neuroimaging

Duration of LOC

PTA

Page 9: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Civilian

Falls 28%

RTA 20%

Object Impact 19%

Assault 11%

Military 11-23% mtbi

59% blast-exposed tbi

Page 10: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

12

24

6 Wakefulness

Stage 1-2 sleep

REM sleep

18.00 20.00 22.00 24.00 02.00 04.00 06.00 08.00 10.00 12.00 14.00 16.00

MT

W

REM

1

2

3/4

Time

Sle

ep

sta

ge

REM sleep

18

Adapted from Rogers et al. Sleep. 1994;17:590.

Stage 3-4 sleep

Page 11: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

waves are small and irregular resembling wake state

bursts of eye activity.

Increase

•Blood pressure, pulse

•Breathing irregular

•oxygen consumption

Atonia and paralysis

Penile, clitoral erections.

Loss of temperature regulation:

•shivering and sweating cease

Page 12: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

N1

•Transition from alpha waves (8Hz to 13 Hz) to theta waves (4Hz to 7 Hz)

•Drowsy sleep.

•Hypnogogic) myoclonus or hallucinations.

N2

•Conscious awareness of the external environment disappears.

•Muscle activity decreases.

•Blood pressure, heart rate, secretions and metabolism decrease.

N3

•Deep sleep

•Parasomnias

Page 13: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Broad range reported including:

Insomnia

Hypersomnia

Sleep Apnoea

Periodic limb movements

Narcolepsy

Specific:

Snoring, nightmares, poor sleep efficiency

Delayed sleep onset, poor sleep quality

Early awakenings

EDS

Page 14: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

68% acute recovery and rehabilitation

Association with being in PTA

50% chronic sleep disturbance

Insomnia

Hypersomnia

OSA

EDS

Tiredness or daytime drowsiness after insufficient sleep or sleep disruption

Hard to disentangle EDS and fatigue MAKLEY, 2008

Page 15: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Insomnia 29%

Hypersomnia 28%

Obstructive Sleep Apnoea 25%

Periodic Limb Movements 19%

Narcolepsy 4%

Mathias, Alvarao Sleep Medicine 2012

Page 16: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Sleep disturbance Overall 5.59 <.001

Sleep disorders

Insomnia 9.94 <.001

Hypersomnia 8.38 <.001

Obstructive sleep apnoea 15.51 <.001

Periodic limb movements 2.95 .003

Narcolepsy 17.11 <.001

Sleep problem

Snoring 3.56 <.001

Insomnia 11.8 <.001

Sleep maintenance 8.96 <.001

Sleep efficiency 4.93 <.001

Sleep initiation 3.80 <.001

Nightmares 7.43 <.001

Excessive daytime sleepiness 15.27 <.001

Early morning awakening 9.76 <.001

Sleep walking 4.85 <.001

Mathias, Alvarao Sleep Medicine 2012

Page 17: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Primary sleep parasomnias REM

REM sleep behaviour disorder most common parasomnia in TBI ~ 10-15%

NREM Disorders of arousal

Sleep walking ~ 9% Sleep eating ~3%

Either Rhythmic Movement disorder

RLS and PLMS

PLMS in TBI ~ 19% Mathias et al 2012

Enuresis Bruxism

Verma et al 2007

Page 18: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Self-reported problems at variance with objective measures

Polysomnography:

Longer sleep-onset latencies

Increased night-time awakenings

Increased SWS

Changes in REM sleep

Results vary

No differences between tbi and healthy controls

(sleep architecture and sleep continuity) OUELLET & MORIN, 2006

Page 19: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Lower cost alternative to PSG

Wrist watch like device

Continuous record of motor activity

Caution – spasticity, paresis, impulsivity, agitation

Poor sleep efficiency in patients in PTA

Increased time spent asleep>6 months post-injury

Circadian rhythm disturbance in mild tbi BAUMANN, 2007

Page 20: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Clinical Interview

PSG

Actigraphy

Sleep Diary

Maintenance of Wakefulness Test (MWT)

Objective assessment of capacity to remain awake

No sig difference tbi v controls (Beaulieu-Bonneau,2012)

Pittsburg Sleep Quality Index (PSQI)

Epworth Sleepiness Scale

Page 21: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

PSQI

Self-report

>8

Insomnia

ESS

Self-rate likelihood of dozing or falling asleep in specified sedentary situations

>=10 [0-24] indicator of EDS

Page 22: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

PSQI – poor sleep quality in mild to severe tbi

(Cantor, 2012)

High EDS scores in some studies with moderate to severe tbi

(Ponsford, 2013)

Findings not universal and depend on sample size

Page 23: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

65 patients with tbi assessed at 6 months post-injury

72% sleep-wake disturbance

Subjective EDS (28%)

Objective EDS (25%)

Fatigue without EDS (17%)

Hypersomnia (22%)

Insomnia (5%)

Page 24: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Earlier bedtimes

Longer sleep-onset latency

Reduced sleep efficiency

Greater total sleep duration and time in bed

Longer and more frequent daytime naps

Mild to severe tbi

3 months to 11 years post-injury

(Ponsford’s group, Australia)

Page 25: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

various

Reduced REM

Increased late REM

Decreased REM latency

12

24

6

Wakefulness

Stage 1-2 sleep

REM sleep

18 Stage 3-4 sleep

Page 26: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Multifactorial

Brain areas associated with sleep regulation

SCN

Hypothalamus

Midbrain

ARAS

NT systems

All vulnerable to tbi

Page 27: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Nofzinger, Sleep Medicine 2005

limbic and paralimbic

hippocampus

amygdala

ventral striatum

basal ganglia

SMA

anterior cingulate

medial prefrontal cortex

,,,,……

…,,.,,,,,,,

,,,,,,,,,,,,,,

,,,,,,,,,,,,,,

,

Page 28: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Locus coeruleus

Raphe nuclei

dorsal, median

LDT, PPT

Peri-aq Grey

Subst. Nigra, VTA

Thalamus

Page 29: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Tubero-mamillary N: TMN

VLPO

SCN

accumbens

Basal forebrain

Page 30: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Lower levels of evening melatonin production (pineal gland) [Shekelton, 2010]

Possible disruption of circadian regulation

(Ayalon, 2007)

Reduced cortical excitability using tms, similar to narcolepsy associated with objectively measured EDS 3 months after mild /moderate tbi [Nardone, 2011]

Possible deficiency in hypocretin/orexin NT system

Page 31: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Pain

Depression

Anxiety

Fatigue

Increased daytime napping night-time sleep quality

Page 32: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Commonly reported

Symptom not diagnosis

Definition and measurement hard to operationalize

Multidimensional construct

Aaronson (1999):

‘the awareness of a decreased capacity for physical and/or mental activity due to an imbalance in the availability, utilization, and/or restoration of resources needed to perform activity’

Page 33: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Physiologic fatigue v. Psychological

Central v. Peripheral

Primary v. Secondary

Psychological fatigue:

‘A state of weariness related to reduced motivation, prolonged mental activity, or boredom that occurs in situations such as stress, anxiety or depression’

The subjective experience of fatigue is likeley a combination of these factors

Page 34: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Various aspects measured

Severity

Impact on daily activities

Associated feelings

No scale specifically for these aspects after tbi

Several scales sensitive to fatigue in tbi population

Page 35: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Visual Analogue Scale for Fatigue (VAS-F)

Subjective, Single point, 18-item

Can measure fatigue at different times of the day, or in response to activity/intervention

Fatigue Severity Scale (FSS)

Behavioral consequences of fatigue

Impact of fatigue on daily living

9 items on a 7-point scale

Barrow Neurologic Institute Fatigue Scale

10 items, 7-point scale

Page 36: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Global Fatigue Index

Multidimensional Assessment of Fatigue

Causes of fatigue questionnaire

Self-report

Few/none validated objective measures in tbi

Search for an objective marker continues

Page 37: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Wide range [21-73%]

Fatigue may decline in the first 6-12 months post injury in moderate – severe tbi but then remain static [Ponsford, 2012]

Even after 10 years significant symptom reporting [Zumstein , 2011]

Considerable individual variation over time

Daytime variation

Progressive increase in fatigue after awakening: reverse of health normals [Beaulieu-Bonneau, 2012]

Page 38: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Group Fatigue (%)

Control 30.6

mtbi 35.1

Mod tbi 32.4

Sev tbi 57.7

[Masson, 1996]

N=231 at 5 years

Page 39: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Cardiac – e.g. Heart failure

Metabolic- e.g. vit D def

Endocrine – e.g. hypopituitarism

Neurologic – e.g. MS

Psychiatric – e.g. Depression, anxiety, PTSD

Infection – e.g. EBV

GI – e.g. Coeliac

Neoplastic

Other

Page 40: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

AED

Antihistamines

Antipsychotics

AD

Steroids

Antiarrhythmics

Antiemetics

Page 41: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Primary fatigue – diffuse neuronal injury

Damage to systems that control arousal, attention, response speed

ARAS

Limbic system

Anterior cingulate

Medial frontal

Basal ganglia

[Chaudhuri & Behan, 2000]

Page 42: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Fatigue – result of increased effort required to manage daily activities in the presence of cognitive difficulties

Expending more effort at greater cost

Tonic v phasic arousal

Baseline arousal/alertness

Arousal in response to stimuli

ARAS involved in phasically turning on cortical tissue in an efficient manner

So PTF: inability to activate but also efficiently sustain and recruit cortical tissue

Page 43: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

GH deficiency reported in a higher than average proporotion of tbi cases [Englander, 2010]

Lower levels of CSF hypocretin-1 [Baumann, 2009]

Hypocretin levels tend to normalise beyond the acute post-injury stage [Baumann, 2005]

Insulin growth factor -1

Adrenal deficiency

Testosterone deficiency

Page 44: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Sleep disorders

Some tired patients do not have any sleep disorder

All patients with sleep disorder do not have fatigue

Depression

Prevalence after tbi variable [6-77%]

Mental effort seems to correlate with fatigue

Correlation between anxiety and fatigue

Page 45: Dr Mayur Bodani Consultant Neuropsychiatrist Raphael ... · damage to brain tissue caused by an external mechanical force, as evidenced by loss of consciousness, post-traumatic amnesia,

Impact on rehabilitation

Constraint on day to day living

Employment

Energy for social activities

Confinement at home

Depression

Effective treatments are limited

Pharmacologic and non-pharmacologic treatments