Disorders of Consciousness:Individualized Assessment Methods

John Whyte, MD, PhDMoss Rehabilitation Research Institute

&

Thomas Jefferson University

Topics to be Covered

Challenges to reaching accurate diagnoses and assessing recovery in VS/MCS

The role of standardized assessment procedures

The role of individualized assessment procedures

Case examples of individualized assessment protocols

Assessment:Challenges to Accurate Assessment

Behavior is highly variable from hour to hour and day to day

Available indicators are generally very simple behaviors that may not be indicators of consciousness (e.g., blinking, eye movements)

Clinicians and caregivers are not objective “integrators” of a set of observations: memory limitations and emotional factors

Case Examples of Assessment Difficulties:

Record review for medical legal purposes of a patient in treatment for over a year

Assessment of a patient living at home: VS, MCS, or higher level?

Standardized Assessment Approaches

“Macro” assessment scales: FIM DRS GOS/ GOS-E All require an inference about level of

consciousness but do not specify how to arrive at that inference

Considerable recovery is possible without major impact on scores

Standardized Assessment Approaches (cont.)Standardized assessment scales appropriate for

VS/MCS patients Coma Recovery Scale-Revised (CRS-R) Coma Near Coma Scale Western Neuro Sensory Stimulation Profile (WNSSP) Disorders of Consciousness Scale (DOCs)

All are more fine-grained, sensitive to changeThey vary in terms of how well indicators of

consciousness are operationalizedCan a single assessment provide a diagnosis?

Role of Standardized Assessment

“Macro” scales: for use in the acute stage when significant recovery is likely; useful for program evaluation, discharge and therapy planning, research

“Micro” scales: acutely, for use in conjunction with “macro” scales; post-acute for stand-alone use for diagnosis (particularly in the absence of promising behaviors), program evaluation, therapy planning

Quantitative Individualized Assessment (QIA)

Based on the principles of single subject experimental design

Intended to answer specific clinical questions and clarify the meaning of particular behaviors that may be controversial (like those discussed in the case examples)

May provide a diagnosis (VS vs. MCS in the process)Useful for monitoring the progress in those behaviorsUseful for guiding treatment approaches

How Does QIA Address the Challenges to Accurate Assessment?

Variability Standardize the assessment conditions Increase the “sample size”

Simple behaviors of ambiguous significance Develop appropriate experimental controls for

non-conscious possibilitiesObserver bias, memory limitations

Operationalize assessment conditions and response scoring

Check inter-rater reliability

The QIA Process used in the MossRehab Responsiveness Program

Initial general clinical evaluation and observation of behaviors, elicit family beliefs

Team meeting to identify questions and clinical priorities

Develop individualized assessment protocol in pilot form

Revise the protocol if necessaryFormal data collection by all disciplinesPeriodic data review, team discussion,

termination or modification of protocol

An Introductory Example

Does the patient make arm movements in response to verbal commands?

The patient appears to move his arm to command inconsistently.

Hypothesis: The patient’s arm movements will occur more often after verbal commands than after silence or contrasting commands.

Define “arm movement”, standardize commands, positioning, initial arousal interventions

Arm Movements to Verbal Command

COMMAND RESPONSE

Moves Arm None

Move Arm 40% (34/84) 60% (50/84)

Hold Still 43% (36/84) 57% (48/84)

Observe 29% (24/84) 71% (60/84)

How Do We Select the Question(s)?

Perceived importance by family and team members

Logical sequenceCurrently available behaviors

How Do We Select the Specific Behaviors and Design the Control Conditions?

Review injury history, neuroimaging, other relevant studies (e.g., ERPs, EMGs, etc.)

Observe for behaviors that occur with some frequency but not extremely frequently

Consider possible reasons for failure other than unconsciousness (e.g., deafness, blindness, aphasia)

Types of Evaluations Successfully Conducted

Patterns of alertness and sleep Patterns of restlessness and agitation Visual statusLanguage comprehension and ability to

follow commandsAbility to engage in simple communication

tasks

Successful Evaluations (cont.)

Types of cuing that result in the best performance

Ability to persist in tasks and whether specific types of cues can promote persistence

Whether certain types of grimacing or moaning are indications of pain

Whether patients recognize family members and/or respond to emotional themes

Some Additional Case Examples

Is the patient’s kicking spontaneous or related to the environment?

The patient had spontaneous kicking of both legs.

Hypothesis: The patient’s kicking is volitional and related to visual recognition of objects that can be kicked.

Responding to Environmental Cues

Response STIMULUS None Left

Kick Right Kick

None 90% (47/52)

8% (4/52)

2% (1/52)

Left Ball 26% (14/54)

47% (25.5/54)

7% (14.5/54)

Right Ball

29% (16/55)

4% (2/55)

67% (37/55)

(Total) 77 31.5 52.5

Can the patient see?

The patient appears to intermittently fixate and track visual stimuli.

Hypothesis: If the patient can see, she should orient to a visual stimulus more often than to nothing, and should orient more often to a complex visual stimulus than a simple one.

Visual Assessment

Stimulus Looks L Looks R No Resp. P/- 9 2 9 -/P 1 12 7 C/- 6 1 13 -/C 0 10 10 P/C 2 7 11 C/P 0 8 12

Can the patient use finger and thumb movements for Yes/No communication?

The patient can flex R thumb and index finger independently, reasonably consistently on command to “Show me a Yes” or “Show me a No”

Hypothesis: If the patient can use these finger movements to communicate, there should be a relationship between yes/no finger movements, and correct answers to yes/no questions

Yes/No Communication

RESPONSE

QUESTION Yes No NR

Yes 26 2 12

No 13 11 16

Evaluation of Treatment Effects

No treatments are proven to enhance recovery.

Can we use the RP assessment methods to prove the value of treatments for individual patients?

We hoped to use the same single subject assessment methods to answer these questions about whether a drug or other treatment improves performance.

Challenges to Individualized Assessment of Treatment

Variability of performanceSpontaneous recoveryTime taken for certain treatments to

workShort length of stay

Three Basic Assessment Designs

A-BA-B-AA-B-A-B-A-B-A-B-A…

(where A = no treatment; B = treatment of interest)

A-B Design

TIME (DAYS)

PERFORMANCE

A-B-A Design

TIME (DAYS)

PERFORMANCE

A-B-A-B-A-B Design

TIME (DAYS)

PERFORMANCE

How Successfully Can We Evaluate Treatment Effects?

A-B: almost neverA-B-A: rarely done and rarely

conclusiveA-B-A-B-A-B…: strongest design, but

not feasible with most treatments; many treatment reversals may be needed if there is great variability

Meta-Analysis of a Set of QIA Assessments in VS/MCS Patients

R. Martin, J. Whyte (in press)

A-B-A-B:Methylphenidate & Responding

RRDIFSC

.31.25.19.13.060.00-.06-.13-.19-.25

8

6

4

2

0

Std. Dev = .11

Mean = .02

N = 23.00

A-B-A-B:Methylphenidate and Accuracy

ACCDIFSC

.38.31.25.19.13.060.00-.06-.13-.19

8

6

4

2

0

Std. Dev = .13

Mean = .02

N = 23.00

Management Structure

Typical interdisciplinary team responsible for patient treatment (including many other medical and physical priorities)

Assessment support team: specially trained Neuropsychologist, data clerk, working in collaboration with JW.

QAI team leads protocol design in collaboration with clinical team; all team members collect data

Reporting back to team with group decisions about next steps

ConclusionQIA methods are highly successful in assessmentQIA methods, within the reality constraints of the

inpatient unit, and LOS, rarely produce definitive results re: treatment

QIA methods can answer specific questions of clinical concern, not answered by standardized scales; may be used in conjunction with those scales

We must rely on traditional group studies to advance our knowledge of treatment efficacy for this patient population

References

Whyte J, DiPasquale M: Assessment of vision and visual attention in minimally responsive brain injured patients. Arch Phys Med Rehabil 76(9):804-810, 1995

Phipps E, DiPasquale M, Blitz C, Whyte J: Interpreting responsiveness in persons with severe traumatic brain injury: beliefs in families and quantitative evaluations. J Head Trauma Rehabil 12(4):52-67, 1997

Laborde A, Whyte J: Update on Pharmacology. Two dimensional, quantitative data analysis: its role in assessing the functional utility of psychostimulants in minimally conscious patients. J Head Trauma Rehabil 12(4):90-92, 1997

Whyte J, Laborde A, DiPasquale MC: Assessment and treatment of the vegetative and minimally conscious patient. In Rosenthal M, Griffith ER, Kreutzer JS, Pentland B (eds.), Rehabilitation of the Adult and Child With Traumatic Brain Injury (3rd Ed.), Philadelphia: F.A. Davis, 25:435-452, 1999

Phipps E, Whyte J: Medical decision-making with persons who are minimally conscious. Am J Phys Med Rehabil 78(1):77-82, 1999

Whyte J, DiPasquale M., Vaccaro M: Assessment of command-following in minimally conscious brain injured patients. Arch Phys Med Rehabil 80:1-8, 1999

References (cont.) Giacino J, Ashwal S, Childs N, Cranford R, Jennett B, Katz D, Kelly J, Rosenberg J,

Whyte J, Zafonte R, Zasler N: The minimally conscious state: Definition and diagnostic criteria. Neurology 12;58(3):349-353, 2002

Whyte J: Valutazione quantitative dei pazienti in stato vegetativo o minimamente responsive “Quantitative assessment of vegetative and minimally conscious patients”. MR Giornale Italiano Di Medicina Riabilitativa, 17(4):31-37, 2003

Giacino JT, Kalmar K, Whyte J: The JFK coma recovery scale-revised: measurement characteristics and diagnostic utility. Arch Phys Med Rehabil, 85(12):2020-2029, 2004

Giacino J, Whyte J: The vegetative and minimally conscious states: current knowledge and remaining questions. The J Head Trauma Rehabil, 20;(1):30-50, 2005

Whyte J, Katz D, Long D, DiPasquale MC, Polansky M, Kalmar K, Giacino J, Childs N, Mercer W, Novak P, Maurer P, Eifert B: Predictors of outcome and effect of psychoactive medications in prolonged posttraumatic disorders of consciousness: A multicenter study. Arch Phys Med Rehabil, 86;(3):453-462, 2005

Martin RT, Whyte J: The effects of methyphenidate on command following and yes/no communication in persons with severe disorders of consciousness: a meta-analysis of n-of-1 studies. Am J Phys Med Rehabil (in press)

General Discussion

A Multicenter Prospective Randomized Controlled Trial of the Effectiveness of Amantadine Hydrochloride in Promoting Recovery of Function Following Severe Traumatic Brain Injury:

“The Amantadine Study”

Study Participants

Participants: patients with traumatic brain injuries resulting in severe disorders of consciousness

180 participants, across 8 facilities in the United States and Europe.

Aims of the study

To determine whether amantadine improves functional recovery in patients with severe disorders of consciousness

To determine whether any amantadine-related gains in function are maintained after the drug is discontinued