Part II: Neuropsychological Tests: Applications and Limitations (Roberta F. White, PhD) I. Introduction In order to provide a background to understanding the utility of neuropsychological test measures in the assessment of central nervous system damage resulting from exposure to neurotoxicants, the following topics will be discussed. Outline I.
Neuropsychology: Background and Definitions
II.
Application of Neuropsychological Tests to Assessment of Patients Exposed to Neurotoxic Chemicals A. B. C. D. E. F. G. H.
III.
Validation of tests Classification of brain damage due to neurotoxic chemicals Test batteries used in research settings Test batteries used in clinical settings Neuropsychological tests Scoring of Neuropsychological tests Differential diagnosis Limitations of neuropsychological tests
Case Material
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II. Neuropsychology: Background and Definitions 1. Definition of neuropsychology •
Neuropsychology is the study of the relationship between behavior and brain structures, i.e., the investigation of specific behaviors which are mediated by specific brain structures.
2. Neuropsychological Assessment •
Clinical neuropsychological assessment involves the evaluation of cognitive and other behavioral functions to define abnormalities attributable to CNS dysfunction, usually through the use of psychological tests.
•
The use of neuropsychological tests allows quantification of behavioral abnormalities.
3. The development of neuropsychological instruments for the measurement of function in specific brain areas arose out of: Early Discoveries in Behavioral Neurology/Neuropsychology •
1800’s: Discovery that patients with lesions in specific parts of the brain showed very specific types of behavioral and functional changes. Broca’s area: Third frontal convolution (posterior inferior left frontal lobe) – Functional correlate: expressive speech – Wernicke’s area: Left posterior portion superior temporal gyrus – Functional correlate: speech comprehension –
This lead to the concept of cerebral specialization: •
Specific brain structures and brain systems mediate specific intellectual and behavioral functions.
Neuropsychological tests can be defined as: •
Behavioral tasks used to measure functions mediated by brain structures.
When the field of neuropsychology began, neuropsychological tests were used for the following purposes: •
Localization of brain damage to specific parts of the brain: - Strokes - Tumors - Purpose: neurosurgical and other interventions
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Differential Diagnosis, such as – Existence of structural brain damage after closed head injury – Existence of dementing disorders
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“Dementia vs. depression”
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Description of functional deficits following brain damage
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Therapeutic, treatment planning
Neuropsychological tests have several advantages, including: •
Standardization of test administration
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Normative scores
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Validation
Sources of validation of these tests are especially important in understanding their contribution to the assessment of brain damage. These include: •
Focal brain lesions
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Specific neurologic disorders Alzheimer’s disease, other primary progressive dementias – cerebrovascular disease – Parkinson’s disease, Huntington’s disease – multiple sclerosis – aphasic syndromes – syndromes related to traumatic brain injury –
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Specific psychiatric disorders schizophrenia – major depression – post traumatic stress disorder –
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Developmental disorders extremes in IQ – learning disabilities – attention deficit disorder – cerebral palsy –
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Motivational disorders malingering – embellishment – “Ganser’s syndrome” –
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“Competency”
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Disability, vocational planning
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Rehabilitation needs
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Environmental/Occupational Illness Diagnosis toxicant-induced encephalopathies – multiple chemical sensitivity – chronic fatigue syndrome –
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Neuropsychologists generally classify their tests in terms of the domains of function that are the focus of each test. The main domains considered by neuropsychological tests include the following: •
Motor: Speed and dexterity in completing tasks, usually using the hand.
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Attention: Capacity to focus on incoming stimuli; includes vigilance, tracking, and capacity to divide attention between competing stimuli.
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Executive function: Ability to organize stimuli, develop strategies for information processing and to reason.
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Language function: Basic linguistic functions, including phonemic and semantic processing
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Verbal abilities: Ability to carry out language-mediated tasks.
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Visuospatial function: Processing of nonverbal information such as visual designs, visual constructions and geographic information; includes sequencing, organization (mental) and constructional ability.
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Memory: Anterograde memory function involves encoding, storing, retrieving and retaining new information. Retrograde memory function refers to the ability to recall information learned in the past.
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Mood/personality: Includes temporary and characterologic mood states and characterologic personality traits or tendencies.
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III. Application of Neuropsychological Tests to Assessment of Patients Exposed to Neurotoxic Chemicals A. The validation of neuropsychological test instruments with regard to focal brain damage is important in the neurotoxicologic setting because individual neurotoxicants are known to affect specific brain structures. Examples of brain regions known to be susceptible to neurotoxicants include the following: • • • • • • •
Hippocampus Basal ganglia Subcortical white matter Frontal lobes Occipital lobes Cerebellum Diffuse brain damage (children)
B .Brain damage from exposure to neurotoxic chemicals can be classified using the following system adapted from the WHO criteria for diagnosis of solvent encephalopathy. This system considers the effects of acute exposure separately from those of chronic exposure. I. Acute organic mental disorders a. Acute intoxication 1. Duration: minutes 2. Residua: none 3. Symptoms: CNS depression, psychomotor or attentional deficits b. Acute toxic encephalopathy 1. Symptoms: confusion, coma, seizures 2. Pathophysiology: cerebral edema, CNS capillary damage 3. Residua: permanent cognitive deficit may occur II. Chronic organic mental disorder a. Organic affective syndrome 1. Symptoms: mood disturbance (depression, irritability, fatigue, anxiety) 2. Duration: days to weeks 3. Residua: none b. Mild chronic toxic encephalopathies 1. Symptoms: fatigue, mood disturbance, cognitive complaints 2. Course: insidious onset 3. Duration: months to years 4. Cognitive deficits: may include attentional impairment, motor slowing or incoordination, visuospatial deficits, short-term memory loss
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c.
5. Residua: improvement may occur in absence of exposure but permanent mild cognitive deficits can be seen Severe chronic toxic encephalopathies 1. Symptoms: cognitive and affective change sufficient to interfere with daily living 2. Cognitive deficits: same as in mild chronic toxic encephalopathies but more severe 3. Neurologic deficits: abnormalities seen on neurophysiologic measures (e.g., CT, EMG, MRI, EEG) 4. Course: insidious onset, irreversible 5. Residua: permanent cognitive dysfunction
C. The application of neuropsychological methodology in the research setting (where the purpose of testing is to examine exposure-effect relationships) is quite different from application in the clinical setting (where one wishes to render a diagnosis). In the research setting, the following criteria guide selection of a test battery: •
Sensitivity to neurotoxicant(s)
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Psychometric properties
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Sensitivity to central nervous system dysfunction
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Developmental specificity
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Overview of cognitive functions
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Sampling of underlying processes
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Multiple output modalities
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Theoretical constructs
1. A number of batteries have been proposed for use in research setting. Including: •
World Health Organization
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Agency for Toxic Substances and Disease Registry
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Boston Battery
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Pittsburgh Battery
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San Francisco Battery
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San Diego Battery
2. Computer-administered tests have attracted considerable interest as a simple way to gather behavioral data in the research setting. The Neurobehavioral Evaluation System is probably the most widely used battery of this type in the United States. It includes the following tasks: •
Neurobehavioral Evaluation System: NES2 (& NES3) – Finger Tapping – Hand-eye Coordination 8AC.001-73
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(Tracing Task) Simple Reaction Time Continuous Performance Test (letters, animals) (Trails) Digit Spans (Visual Spans) Pattern Recognition (Incomplete Figures) (Naming) Pattern Memory Verbal Paired Associates (IR, DR) List Learning (IR, DR, Recognition) Profile of Mood States (Nonverbal Analogue Profile of Mood States)
D .In the clinical setting, neuropsychological test batteries should ideally address the following criteria: •
Sensitivity to neurotoxicant(s)
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Developmental appropriateness
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Clinical validation
1 .As we have mentioned, clinical and research settings are different in focus and in the type of outcome that one can expect to generate. Diagnosis of toxicant induced CNS dysfunction requires that test scores on tasks known to be vulnerable to exposure to the toxicant in question are at impaired levels (> 1 S.D. below expectation) based on estimates of the patient’s premorbid function. However, in the research setting, doseresponse relationships are the basis for conclusions regarding exposure effects; these may be found with outcome scores that might generally be considered “normal” •
Research focus: dose-effect or exposure-effect relationships
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Clinical focus: differential diagnosis
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Contrast in test scores required for “significant results”
2. The clinical neuropsychological assessment of patients includes the following procedures: a. Interview •
Reason for referral
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Presenting complaints
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Cognitive function
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Neurologic symptoms
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Medical history
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Psychiatric symptoms, history
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Current medications
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Substance use/abuse
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Personal history
E .Neuropsychological Tests: consisting of tasks selected from the following domains: Test Name
Description Tests of General Intelligence
1.
Wechsler IQ tests (WAIS-R, WAIS-III, WISC-III, and WPPSI-R)
Omnibus IQ measures
2.
Stanford Binet Intelligence Scales, 4th Edition
Omnibus IQ measure
3.
Raven Progressive Matrices
Test of visual reasoning
4. Kaufman Assessment Battery for Children
Omnibus IQ measure
5. Bayley Scales of Infant Development, Omnibus test of cognitive and motor 2nd Edition
function
Tests of Academic Knowledge 1.
Peabody Picture Vocabulary Test- Single word comprehension 3
2.
Wide Range Achievement Test-3
Academic skills in arithmetic, spelling, reading
3.
Gates-MacGinnitie Reading Test
Reading vocabulary and comprehension
4.
Vocabulary (NES)
5.
Wechsler Scales: Information
Multiple choice format vocabulary knowledge computer- assisted) Information usually learned in school
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Tests of Attention, Vigilance and Tracking 1. Digit Span (Wechsler IQ and Memory test)
Digits forward and backward
2.
Visual Spans (Wechsler Memory Scale)
Visual spans forward and backward
3.
Arithmetic, Wechsler IQ Tests
Oral calculations
4.
Trail-Making Test
Connect-a-dot task requiring sequencing and alternating sequences
Test Name 5. Continuous Performance Test 6.
Paced Auditory Serial Arithmetic Test
7.
Stroop
Description Acknowledgement of occurrence of critical stimuli in a series of orally or visually presented stimuli Serial calculation test Test requiring subject to divide attention between word names and colors
Tests of Executive Function 1.
Wisconsin Card Sorting Test
Requires subject to infer decision-making rules
2.
Categories Test
Inferential reasoning test
3.
Wechsler Scales a. Comprehension b. Similarities
4.
Letter Number Sequencing (Wechsler IQ and Memory Scales)
5.
Matrix Reasoning (Wechsler IQ)
Proverb definitions, social judgment, problemsolving Inferences of similarities between nominative words Remember and re-sequence numbers and letters
Reasoning
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Tests of Verbal and Language Function Verbal 1. Wechsler Vocabulary (also Information, Comprehension, and Similarities)
Verbal vocabulary definitions (see above)
Language 1. Controlled Oral Word Association Word
Word list generation within alphabetical or semantic categories
2.
Naming of objects depicted in line drawings
Boston Naming Test
Tests of Motor Function 1.
Finger Tapping
Speed of tapping with each index finger
2. Dynamometer Test Name
Grip strength with each hand Description
3.
Santa Ana Formboard Test
Knobs in a form board are turned 180ยบ with each hand individually and both hands
4.
Digit Symbol (Wechsler IQ Tests) Coding task requiring matching digits to symbols
5.
Pegboards (Purdue, Grooved)M
Manual dexterity
Tests of Visuospatial Function 1.
Wechsler IQ Tests: a. Picture Completion b.
Picture Arrangement
c.
Block Design
d.
Object Assembly
2.
Hooper Visual Organization Test
3. Rey-Osterreith Complex Figure (copy condition) 4.
Embedded Figures
Identification of missing details in line drawing Sequencing of cartoon frames to represent meaningful stories Assembly of 3-D blocks to replicate 2-D representations of designs Assembly of puzzles Identification of correct outline of drawings of cutup objects Drawing of a complicated visual design Identification of target stimuli within a complex array
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Tests of Short-Term Memory 1.
Wechsler Memory Scale - III Subtests a. Logical MemoriesImmediate and Delayed Recall (IR, DR) b.
Verbal Paired Associates Learning (IR, DR)
Omnibus test of memory and attention resulting in several memory indices Recall of paragraph information read orally on immediate and 20-minute delayed recall with recognition condition Two paired words are presented in a list of pairs; subject must recall second word; test is presented on immediate and delayed recall with recognition
Test Name
2.
Description
b. Facial Memory (IR, DR)
Multiple choice recognition of faces immediately after initial presentation and on DR
c. Family Pictures Tests (IR, DR)
4 family pictures presented; characters, positions, activities reported on IR and DR
d. Visual Reproductions(IR, DR, copy)
Visual designs are drawn immediately after presentation and on delayed recall with recognition condition List learning task
Rey Auditory Verbal Learning Test
3. Selective Reminding Test
List learning task with selective reminding (missed items only)
4. California Verbal Learning Test
Subject is presented with list of 16 words (which can be semantically related) over multiple learning trials, short and long delayed recall
5. Rey-Osterreith (IR, DR)
Complex design is copied and drawn at immediate recall and 20-minute delay
6. Benton Visual Recognition Test
Multiple choice memory for visual designs
7. Peterson Task
Words or consonants are presented and must be recalled after a period of distraction Forced choice picture memory test
8. Test of Memory and Motivation
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Tests of Personality and Mood 1.
Profile of Mood States
2.
Minnesota Multiphasic Personality Inventory
65 single-word descriptors of affective symptoms are endorsed by degree of severity and summed on mood scales True-false responses provided on personality inventory and summed on multiple clinical dimensions
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F. Scoring of Tests. Raw scores are generally converted to normative scores using one of the following types of conversions: – Standard score, mean = 100, s.d. = 15 – T score, mean = 50, s.d. = 10 – Scaled score, age scaled score, mean = 10, s.d. = 3 – Percentiles – Stanines – Age scores – Grade levels G. Differential Diagnosis (and test selection) are based on the referral question, interview responses, history and test results. The usual referral issues in the occupational setting include the following: 1. Usual Referral Question: Patient who has been exposed to a neurotoxicant shows behavioral changes (cognitive/intellectual, affective/emotional, personality). What is the likely cause? 2. Diagnosis: Are observed behavioral changes attributable to neurotoxicant exposure or something else? 3. Differential Diagnosis: If behavioral changes are identified (sometimes they are not) and they are not due to exposure, what is the probable diagnosis? 4. Implications: If attributable to neurotoxicant exposure: a. how severe are the changes or impairments observed? b. how will they affect the patient’s life, employability? c. what is the likely prognosis for recovery? 5. Recommendations: What further diagnostic procedures and treatment plans are indicated? When carrying out diagnosis of toxicant induced CNS damage, the clinician must first model an impression of the patient’s premorbid or native ability patterns. This can be done using: •
“Hold Test” Performance – academic tests – other hold tests
•
School Records
There are several patterns of native ability profiles seen in the general population. These include: Consistent Overall Intellectual Level • Very Superior Intelligence – Verbal IQ = 130
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Performance IQ = 132 Reading Scaled Score = 130 Arithmetic Scaled Score = 135
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Borderline Intelligence – Verbal IQ = 70 – Performance IQ = 78 – Reading Scaled Score = 78 – Arithmetic Scaled Score = 71 Nonverbal Learning Disability – Verbal IQ = 145 – Performance IQ = 95 – Reading Scaled Score = 140 – Arithmetic Scaled Score = 90 Verbal Learning Disability – Verbal IQ = 80 – Performance IQ = 110 – Reading Scaled Score = 75 – Arithmetic Scaled Score = 112 In children exposed to neurotoxicants, estimating a native ability profile can be quite difficult. The earlier the exposure occurs, the more difficult the task becomes, especially if there has been exposure prenatally. However, two clues to this estimation include: •
Parent’s intellectual patterns
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Pre-exposure academic achievement of child
The process of differential diagnosis begins with identifying whether there are impairments in test performance, including: •
Types of abnormalities (processing deficits, domains in which deficits are identified)
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Severity of abnormalities
and the domains in which they occur: •
General Intelligence
• Verbal/language skills
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Attention
• Visuospatial abilities
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Executive function
• Short-term memory
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Motor Skills
• Mood/personality/prosody
In addition, the neuropsychologist looks at the: •
Patterns of deficits across behavioral domains
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Specific cognitive processing deficits uncovered in assessment
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Localization
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History
In occupational settings, common differential diagnostic issues include: • Neurotoxicant-induced encephalopathy vs: – primary dementia – cerebrovascular dementia – learning disability, attention deficit disorder, limited intellect – psychiatric disorder or factitious disorder – multiple chemical sensitivity •
Neurotoxicant-induced Parkinsonism vs. idiopathic Parkinson’s disease
The neuropsychological test report summarizes assessment findings, relevant history, and recommendations for patient follow-up and care. These may include:
H.
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Medical: neurological evaluation, laboratory studies (thyroid, VDRL, HIV, drug levels), EEG, MRI, nerve conductions, ophthalmologic examinations
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Vocational: IH evaluations, removal from exposure, follow-up testing, vocational planning, disability
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Academic: tutoring
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Psychiatric: pharmacologic intervention, psychotherapy, cognitive rehabilitation
Limitations to Neuropsychological Diagnosis include: 1. 2. 3. 4. 5. 6.
Floor effects among patients with low intelligence Technique best at localization: problems of overlapping pathology Subtle deficits impossible to detect in patients who embellish Cultural limitations (language, norms) Limitations in assessing subtle effects in patients without pre-exposure testing Successful recovery from encephalopathic events related to exposure
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IV. Case Material Case 1: Moderate-to-severe solvent encephalopathy This patient was 55 years old at the time of referral. Because of memory loss and behavioral change, he had been diagnosed 2 years earlier as having AD by a neurologist who noted that the presentation of the dementia was unusual. He was brought in by a family member who had begun working with AD patients after his diagnosis; she thought he was different from them, particularly because his cognitive status was not declining. He had a history of exposure to high levels of mixed solvents at work on a daily basis, including TCE. He used these solvents in cleaning equipment in a factory and was exposed to open vats of the chemicals. In fact, part of his job was to be lowered into vats which had contained TCE for the purpose of cleaning the vats. He did not wear a respirator. Exposure occurred during the 1950s through the 1970s. He retired in 1978 when he was no longer able to function effectively at work. He was tested around 1984. Test results suggested normal permorbid function and he performed normally on tasks that are robust following solvent exposure, including tasks assessing: • Academic information • Vocabulary definitions • Naming • Oral reading • Writing However, he had moderate-severe deficits on tasks measuring executive function, problem solving, attention, and visuospatial function. Short-term memory impairment was severe, and caused impairments in ability to recall information from the period of greatest exposure: • Abnormal findings: WAIS-R Similarities, Comprehension – WAIS-R Digit Spans, Arithmetic – WMS-R Mental Control – WAIS-R Picture Completion, Block Designs, Object Assembly – WAIS-R Digit Symbol – Wechsler Memory Scale: new learning, with steep forgetting rates – Albert’s Famous Faces (1960’s and 1970’s) – Diagnosis was moderate-to-severe solvent encephalopathy. When re-tested 3 years later, performance was quite similar and no decline was noted. Case 2: Milld-to-moderate PCE encephalopathy This patient was a 27-year-old woman at the time of initial testing. She was referred for evaluation by her occupational health physician as part of an assessment of health effects of PCE exposure. She had worked for three years at one dry cleaning establishment, leaving it three months prior to evaluation because she was worried
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about symptoms she was experiencing, including dizziness, fatiguability, memory loss, confusion, and intolerance for alcohol. The machine used at the plant for reclaiming PCE was broken, causing unusual amounts of PCE to be released into the air. When she switched jobs, she continued to work as a dry cleaner. Though she felt that the second workplace was much cleaner, she was concerned because she was continuing to experience symptoms. Her evaluation showed the following: • •
•
Estimated native intelligence: average Normal findings: Verbal/language, attention WAIS-R Similarities, Comprehension – Boston Naming Test – Controlled Word Association Test – Writing, Reading – WAIS-R Digit Spans – Abnormal findings: executive, motor, visuospatial, memory, mood Wisconsin Card Sorting – WAIS-R Block Designs, Object Assembly – WAIS-R Digit Symbol – Wechsler Memory Scale: new learning, with steep forgetting rates – Difficult Paired Associate Learning – Profile of Mood States –
Diagnosis of mild-moderate encephalopathy was made, and she stopped working as a dry cleaner, eventually becoming a cashier in a grocery store. At evaluation two and four years after she was initially seen, she showed improvement in cognitive function and mood. At final testing, mild residual problems were seen on Block Designs and Object Assembly, and she had remarkable problems with the Wisconsin Card Sorting Test, but memory function was normal. She said that she herself felt that she had returned to baseline but her husband, who had known her before she began working as a dry cleaner, felt that she was never quite the same. Case 3: Frontal lobe dementia This patient, a 65-year-old man with a master’s degree who worked with solvents as a chemist/technician in a paper factory, was referred for neuropsychological evaluation by his occupational physician, who found his behavior and thinking style to be highly unusual. The physician felt that the differential diagnostic issue might be solvent encephalopathy vs. obsessive/compulsive disorder. The patient himself was unsure what was wrong with him, talked in streams of associative speech that contained many details, and carried with him a briefcase filled with Material Safety Data Sheets and other information about his exposures and his symptoms. His neuropsychological assessment showed the following: • •
Estimated native intelligence: superior (>120) Normal findings: simple attention
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•
Abnormal findings: Moderate: –
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Mild:
verbal/language short-term memory (new learning, retention okay) executive motor visuospatial
His naming of pictures of objects was particularly pathognomic with regard to diagnosis. Some examples of his naming errors include the following: •
Naming errors: octopus: “porcupine” – pretzel: “snake” – snail: “scroll”, “porcupine” – beaver: “rat” – acorn: “kernel” – escalator: “elevator” – pelican: “parrot” – stethoscope: “doctor’s octopus” – sphynx: “mummy” –
This patient’s neuropsychological diagnosis was dementia of the frontal lobe type, a diagnosis that was also rendered by a national dementia center, where he was followed. Case 4: Malingering This patient, who was middle aged at the time of his assessment, had worked for two years in a dry cleaning establishment and reported memory problems to his physician. He was applying for Workman’s Compensation for CNS damage secondary to exposure. Interestingly, his wife was also on Workman’s Compensation. His occupational health physician wondered if any evidence of behavioral impairment would be seen on neuropsychological testing. Test results showed the following: • • •
Estimated native intelligence: high average Normal findings: verbal/language, visuospatial, motor, memory (retention) Abnormal findings: Severe: simple attention – Moderate: new learning – Mild: executive –
In addition, there were remarkable inconsistencies in his performance within tests and among tests assessing the same function. Some examples include these: Could recite only 4 digits forward but remember 17 details from – stories Digits forward = digits backward – 8AC.001-85
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Attention Index 30 points less than IQ, 11 points less than memory index Paired associate learning on 1 task 7/8 on third trial, 0/10 on another task on third trial
This patient was diagnosed officially in his report as having emotional – not neurological – reasons for his memory complaints, though his MD was informed that embellishment or malingering were highly likely. At follow-up interview with the neuropsychologist, he was told that he seemed to have some problems in concentrating but that his brain appeared to be fine. He was enraged that he had not been diagnosed with brain damage. Later it turned out that at another clinic he had almost convinced physicians that he had sarcoidosis, which could not be confirmed on diagnostic tests.
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