Neuropsychological Testing

1. History Taking and Clinical Interview

The questions included in the interview should address information about the patient's current symptoms as well as his or her past medical history. This process can be facilitated by having the patient complete a standardized questionnaire such as the "Boston

Occupational and Environmental Neurology Questionnaire." Information about the patient's performance in school and work should be obtained. It should be determined whether the patient has had any previous psychiatric, neurological, or developmental-academic problems that could affect his or her performance on neuropsychological tests. The patient should also be questioned about the history of his or her immediate family members, including details about education levels and occupations as well as medical and psychiatric histories. Past and present recreational use of drugs, alcohol, and prescribed medications that may affect performance on neurop-sychological tests should be noted. The particulars of the circumstances surrounding the alleged exposure to neurotoxicants must be defined and documented. Material safety data sheets and documentation of current and past exposure levels should be obtained whenever possible.

2. Methods of Neurobehavioral Assessment

The clinical approach to the neuropsychological assessment of cognitive deficits and behavioral changes attributable to exposure to neurotoxicants is essentially the same as that applied to any neuropsy-chological assessment situation. The clinician must be familiar with the expected or likely behavioral effects of the various neurotoxic chemicals found in the workplace and environment to which the patient may have been exposed. An experienced neuropsychologist will be able to carry out the differential diagnostic process of determining the most likely etiology of any deficits that may be revealed by testing.

The clinical neuropsychological evaluation of patients with possible toxic encephalopathy necessitates that the clinician perform a careful and thorough examination of each patient. Many areas of cognitive function must be assessed so that exposure-related effects can be detected and other possible diagnoses comprehensively evaluated and ruled in or out. Because there is overlap between the behavioral effects of exposure to certain neurotoxic chemicals and those associated with developmental disorders (e.g., learning disabilities, attention deficit disorder), psychiatric conditions (e.g., posttraumatic stress disorder, bipolar disorder), neurological diseases (e.g., multiple sclerosis, cerebrovascular disease, primary progressive dementia, parkinsonism), and the exposure to ethanol, medications, and illegal drugs, the test battery must allow for consideration of these alternative or contributing conditions.

The literature on behavioral toxicology includes the results of epidemiologic studies of exposed populations as well as clinical case reports. A number of batteries have been proposed for the assessment of neurotoxic effects of industrial chemicals. It is important to note that, whereas these batteries may be well-suited to the epidemiological investigation of neurotoxic effects, they are too brief and lack some tests essential to the process of making a clinical differential diagnosis. In addition, some of these batteries contain tasks with no available norms upon which a clinical diagnosis could be based. The results from epidemio-logical studies using these test batteries are nevertheless important to the neuropsychologist performing clinical case assessments. They can provide insight into the domains of function expected to be affected and unaffected by exposure to specific neurotoxicants and aid in the selection of appropriate tests expected to be sensitive to the effects of a particular toxic chemical.

There are fundamental differences between epide-miologic and individual clinical testing endeavors. In the epidemiologic setting, tests are designed or selected to ascertain dose-response relationships between the degree of exposure and neurobehavioral outcomes among members of a group of exposed persons. In the clinical setting, one is looking for deficits relative to the expected premorbid level of performance for an individual. In the epidemiologic setting, neuropsycho-logical test scores within the "normal" range nevertheless may support an adverse effect of exposure based on dose-response outcomes. In the clinical setting, however, scores must be at least 1-2 standard deviations below normative expectation for the subject in order to be considered indicative of a deficit. Thus, clinical examinations may require a greater degree of dysfunction in order to conclude that an exposure is having (or has had) an effect than might be seen in the research setting.

The field of neuropsychology has a number of assessment approaches, including the Halstead-Rei-tan method, which typically employs a set battery of tasks, and the behavioral neurology or Process Approach, which employs a flexible battery in evaluating patients with specific kinds of referral issues or who show certain types of processing deficits during the evaluation itself. We have developed a battery of tests sensitive to the effects of neurotoxic chemical (Table II).

The neuropsychologist typically employs tests with which he or she is familiar and uses frequently to examine the toxicant-exposed patient. These tests are generally classified according to the cognitive domains

Table II

Boston Extended Neurotoxicologic Battery: Clinical Version0

Behavioral test

Cognitive domain assessed

WAIS; WAIS-R: WAIS-III Information Vocabulary Comprehension Similarities Digit Spans Arithmetic Picture Arrangement Block Design Object Assembly Digit Symbol WMS-R Information Orientation Mental control Digit Spans Visual Spans Logical memories Verbal Paired Associates Visual Paired Associates Visual Reproductions Figural Memory Continuous Performance Test

Trail-Making Test (A and B)

Wisconsin Card Sort Test FAS-verbal fluency Boston Naming Test Boston Diagnostic aphasia Exam

- reading comprehension subtest Wide Range Achievement Test Boston Visuospatial Quantitative

Battery Santa Ana Form Board Milner Facial Recognition Test Benton Visual Rention Test Difficult Paired Associates Albert's Famous Faces Test Profile of Mood States

Minnesota Multiphasic Personality Inventory

Basic academic verbal skills Verbal concept formation Verbal concept formation Verbal concept formation Attention

Attention and calculation Sequencing and visual spatial Visual spatial Visual spatial Psychomotor speed

Attention and cognitive tracking

Attention (verbal)

Attention (visual)

Verbal memory

Verbal memory

Visual memory

Visual memory

Visual memory

Attention (vigilance) and reaction time Attention, cognitive tracking and sequencing Set formation and set shifting Language Language Language

Basic academic skills Visuospatial

Psychomotor speed

Visuospatial and visual memory

Visual memory

Verbal memory

Retrograde memory

Affect

Personality and affect

"From White, R. F., and Proctor, S. (1995). In "Neurotoxicology: Approaches and Methods'' (L. W. Chang and W. Slikker, eds.), Ch. 46, Academic Press.

they tap. Though no test is so pure that it taps only one type of cognitive processing skill or functional domain, many load heavily on one area of function or another. The most commonly assessed functional domains in neuropsychology include attention, executive function, fine manual motor skills, visuospatial abilities, language and verbal skills, anterograde (short-term) and retrograde memory, and affect and personality. Regardless of the battery of tests used, it is essential that the clinician determine an estimate of premorbid ability patterns for the patient. Any deficits uncovered on neuropsychological testing should be related to this estimate of baseline function. Neuropsychologists are typically interested in academic skills such as reading and arithmetic (which are often helpful in determining premorbid ability patterns) and in motivation to perform well on testing which can be influenced by aspects of secondary gains such as monetary compensations. The reader is referred elsewhere for descriptions of the tasks assessing these domains. The various domains mentioned earlier as well as the expected changes in performance associated with exposure to neurotoxicants are described next to provide additional insight into the neurobehavioral features of toxic encephalopathy.

a. Language-Verbal Function Language and verbal functioning are typically preserved in adults exposed to neurotoxicants. This aspect of cognitive function is relatively resistant to the effects of neurotoxic exposure-induced brain damage compared with dynamic cognitive processes, such as encoding of new memories. This is in stark contrast with the effects of stroke and other focal lesions, which may have profound impacts on language function. However, patients exposed to certain neurotoxic chemicals (e.g., carbon monoxide) may show deficits on tests requiring the application of verbal and language skills. Motor aspects of writing may be affected in those patients with movement disorders (e.g., tremor) resulting from neurotoxic exposure, whereas the grammatical aspects of writing remain intact. Exposure to neurotoxic chemicals is more likely to produce language deficits in children than in adults because disruption of encoding processes occurs during development and, thus, can lead to problems with language acquisition. The severity of the deficits seen depends upon the age of the child at the time of exposure; younger children are more vulnerable.

b. Attention and Executive Function Deficits in attention and executive function may be found on formal testing of patients with exposures to neurotox-icants. Tests of attention measure the following: (1) simple (immediate) attention, i.e., how much information can be grasped at once; (2) divided attention, which is the ability of an individual to attend to more than one task simultaneously; and (3) vigilance or sustained attention, which measures the ability of the subject to remain focused on a single task for long durations of time. Attention deficits impair the patient's ability to selectively focus on relevant stimuli and, therefore, may have a direct effect on concentration and an indirect effect on memory function.

Executive function is a higher order behavioral process involving the ability of the subject to appreciate and respond to complex changes in neurobeha-vioral task demands, including recognizing, maintaining, and shifting set as necessary to carry out such tasks. Cognitive tracking is an aspect of executive function often found to be impaired in those patients exposed to neurotoxic chemicals. Trail making (Trails A and B) is a cognitive tracking task that has been shown to be sensitive to problems associated with exposure to neurotoxic chemicals. Cognitive flexibility is another aspect of executive function that is affected in toxic encephalopathy. Difficulties in cognitive flexibility may be revealed by tasks such as the Wisconsin Card Sorting Test. Although some patients show deficits on tests of both cognitive tracking and cognitive flexibility, other patients exhibit deficits on one but not the other. It is impossible to predict which type of deficit will be seen in a patient with toxic encephalopathy, and it does not appear to be related to the type or severity of the exposure. Patients with severe deficits in executive function may have problems with their activities of daily living.

c. Memory Function Memory can be affected at several levels, including encoding of new information, retrieval of encoded information, ability to inhibit interference during learning and retrieval, and retention of encoded information. Many patients exposed to neurotoxic chemicals have relative deficits on tests of short-term or anterograde memory function compared with retrograde memory or long-term memory function. This dichotomy reflects the sensitivity to neurotoxic exposure-induced brain damage of the complex dynamic processes involved in short-term memory function, particularly encoding processes, and the relative resilience of the previously stored information tapped by tests of retrograde memory function, which is considerably more dependent upon retrieval mechanisms. Because of the divergent pat terns of memory impairment possible following toxic exposure, a rather extensive memory battery is used to assess these patients.

d. Motor Skills Motor function is affected in some patients exposed to neurotoxic chemicals. Patients may show performance deficits on tests sensitive to motor deficits, including Finger Tapping and the Santa Ana Formboard. Motor function deficits can interfere with the patient's performance on many neurobehavioral tests (e.g., Digit Symbol). For example, a patient with bradykinesia may perform poorly on timed tasks measuring performance in domains other than motor function because they simply move more slowly. The neuropsychologist using the behavioral neurology or Process Approach can take into consideration the effects ofmotor deficits on other neurobehavioral tasks and utilize this information in his or her assessment and interpretation of the patient's performance.

e. Visuospatial Abilities Visuospatial deficits are seen following exposure to certain neurotoxicants (e.g., mercury). Performance on tests such as Block Design and the Rey-Osterreith Complex Figure (copy trial) may be below expectation in a patient exposed to neurotoxicants.

3. Strengths of Neuropsychological Tests

Neuropsychological test procedures have some inherent strengths and weaknesses with regard to making clinical diagnosis.

A. They are reliable because they have been standardized with regard to scoring and administration. For this reason, they can be given in the same manner by different clinicians.

B. Normative values are available for these tests so that performance can be judged with regard to level of performance. These norms allow the clinician to compare the patient's performance to that evidenced by persons of the same age and, often, of the same gender and educational achievement. For some tests, norms specific to countries outside of the United States are available, as are norms for specific groups within the U.S. population (e.g., Hispanics).

C. The tests have been well-validated, and a great deal is known about how performance on one test relates to performance on similar tests. In addition, extensive information is available concerning the brain structures that participate most directly in the completion of tasks (brain-behavior relationships revealed by the tasks) and the patterns of performance on the tests among patients with specific developmental, neurological, motivational, and psychiatric disorders.

4. Weaknesses of Neuropsychological Tests

A. In persons with low premorbid intellectual abilities, it can be difficult to identify subtle deficits in function because they are performing at the floor of the tests already (many tasks have high floors).

B. When there is a long delay between exposure and neuropsychological testing, physiological recovery and/or use of compensatory strategies by the patient may occur, obscuring changes in function that may have been evident at the time of exposure. Among patients whom we have seen longitudinally from the time of exposure until several years after exposure ceased, it is clear that for some cases we would not have been able to diagnose the toxicant-related effects or determine the minor residuum of those effects had we not seen the patient early.

C. For some subgroups of patients within the U.S. population, particularly immigrants who do not speak English as a first language, normative values may be unavailable or available only for a limited number of tests.

D. In patients for whom sick-role playing or embellishment is an issue, inconsistencies in test performance or exaggeration of performance deficits may obscure mild or subtle brain dysfunction associated with exposure to toxic chemicals.

E. Conditions with overlapping pathologies can make differential diagnosis difficult. For example, patients with white matter lesions may have multiple sclerosis, a toxicant-induced condition, or both. Similar problems hold for parkinsonism affecting basal ganglia function, which can occur secondary to toxicant exposure, infections, infarcts, or a combination of these brain insults. Cerebrovascular disease is also a problem because it presents with a frontal-subcortical picture on neuropsychological testing similar to that of many toxic chemicals. Furthermore, exposure to certain neurotoxicants (e.g., mercury) that may be associated with hypertension can lead to brain dysfunction.

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