Asperger's Syndrome

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Assistant Editor: Michael S. [ellinek, M.D.

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Asperger's Syndrome FRED R. VOLKMAR, M.D., AMI KLIN, PH.D., ROBERT SCHULTZ, PH.D., RICHARD BRONEN, M.D., WENDY D. MARANS, M.D., SARA SPARROW, PH.D., AND

DONALD ]. COHEN, M.D.

ABSTRACT

This Grand Rounds is concerned with the classification of Asperger's syndrome and its continuity/discontinuity with autism. Information on a 15-year-old with the condition is presented as are data on other family members. The proband exhibited a longstanding pattern of marked deficits in social interaction, motor awkwardness, and unusual, circumscribed interest consistent with a diagnosis of Asperger's syndrome. Both the proband and his father exhibited unusual discrepancies between verbal and performance (nonverbal) cognitive abilities favoring the former. Deficits were observed in the social use of language. Father and son had similar abnormalities on magnetic resonance imaging examination. Potential differences between higher-functioning autism and Asperger's syndrome are important areas for future research. J.

Am. Acad. Child Ado/esc. Psychiatry, 1996, 35(1): 118-123. Key Words: Asperger's syndrome, autism, pervasive developmental disorder, case report.

Introduction: Fred R. Volkmar, M.D.

Although autism is the most widely recognized pervasive developmental disorder (PDD), other diagnostic concepts with important similarities to autism have been identified (Volkmar and Cohen, 1991) and have now been included in DSM-IV (American Psychiatric Association, 1994; Volkmar et aI., 1994). Of these "new" conditions, Asperger's syndrome (AS) has been the most controversial. As originally described by Asperger (1944), this syndrome was characterized by problems in social interaction and motor skills in the context of relatively intact overall cognitive and communication skills. In the original report the cases (all males) exhibited unusual circumscribed interests, e.g., knowing all the train or bus schedules into/out of Vienna. In addition, there often appeared to be similar traits in family members, particularly fathers. Until Wing's influential review (1981), Asperger's concept attracted little interest in the English language literature. Wing noted that some aspects

Accepted May 23, 1995. From the Child Study Center (Drs. Volkmar, Klin, Schultz, Marans, Sparrow, and Cohen) and Diagnostic Radiology (Dr. Bronen), Yale University School of Medicine, New Haven, CT. This article is based on a case presented October 4, 1994; identifjing information has been changed to protect patient confidentiality. The authors are gratefUL to the patient and his Ji:tmi/y fOr their cooperation. Reprint requests to Dr. Volkmar, P.0. Box 201900, New Haven, CT 06520-1900.

0890-8567/96/3501-0118$03.00/0©1996 by the American Academy of Child and Adolescent Psychiatry.

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of the original description warranted modification, e.g., the syndrome could be seen in girls. She also noted some important potential differences from autism, e.g., the relative preservation oflanguage and cognitive skills and the apparent later onset of the condition. In the absence of generally accepted or "official" definitions, AS has been used in very different ways, e.g., (1) synonymously with "highfunctioning autism," (2) in reference to adults with autism, (3) in reference to individuals with "subthreshold" PDD (i.e., PDD not otherwise specified), and (4) in reference to a syndrome that differs from autism in important ways. Despite these inconsistencies, case reports have appeared with increasing frequency (Gillberg, 1989; Klin, 1994; Szatmari et aI., 1990). The ICD-I0 (World Health Organization, in press) draft criteria for research included AS as a category within the PDD class; the validity of the condition, i.e., as distinct from autism, was explicitly noted to be controversial. Eventually DSM-IValso included the condition with a very similar definition to that used in ICD-I0 (Volkmar etal., 1994). AS is now defined on the basis of social deficits and restricted patterns of interest and behavior of the type seen in autism, although there must be no clinically significant delay in language acquisition or in cognitive skills. Motor deficits are not an essential diagnostic feature, although the DSMIV notes that motor clumsiness may be present. Despite the advance represented by official definitions of the condition, controversies continue over its validiry and boundaries (Bishop, 1989). The case presented here appears to us to

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be an example of AS in its most "classic" form and can serve as the focus for discussion. Case Presentation: Ami Klin, Ph.D.

Tom Z. is a tall, stocky 15-year-old. He is the older of two children; his father is a successful engineet and his mother is a secretary. He was born following a term, uncomplicated pregnancy. Apart from a hernia repair in infancy, his medical history is unremarkable. Developmental milestones were within normal limits; Tom talked before he walked. He started nursery school at age 2 Yz years and already had unusual interests which were pursued to the exclusion of other activities. Over the years these interests have included stop signs, arrows, storm drains, and windmills, and, more recently, have changed to clocks, mathematics, and computers. Tom was a self-taught reader by age 3 and was reading adult-level books by age 4. In nursery school he had poor peer relations, talked incessantly about topics of interest only to himself, failed to listen to other children's comments, and was often oppositional and impulsive. At the same time he was aware of his social isolation. A preschool psychological assessment recommended special education placement; various programs were tried with limited success. Tom moved to private schooling and finally home-bound education. Despite precocious academic achievements he continued to have marked problems in social interaction and in the regulation of his behavior. A clumsy and poorly coordinated child, Tom often seemed markedly odd outside home or school settings. In his preoccupation with clocks he might approach a stranger and proceed to reset the person's watch without asking permission and often reset public clocks, e.g., at school. At his first evaluation here, when he was 9Yz years old, Tom had no friends, very limited interpersonal skills, and signs of depression. His parents were then separated. Dr. Volkmar noted that Tom spoke in a monotone. His fascination with clocks pervaded all conversation. His poor social judgment was repeatedly observed, particularly in his description of interactions with peers. Nonverbal cues of social context, e.g., gestures, facial grimaces, emphasis of voice, and nonliteral communications, were limited. A positive history for similar problems was noted in Tom's father. Mr. Z. always carried a small notebook with him to write down the names of important persons he met since, as he reported, "I can never remember people's faces; I can only remember names when I write them down." The impression was that Tom exhibited AS. Tom's second evaluation was conducted here 2Yz years later, when he was 12 years old. It followed a brief hospitalization following what school staff thought to be a suicidal gesture but which seemed to us to more likely reflect his social and behavioral rigidiry (he had "frozen" in a crosswalk

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when the signal light changed to "Don't Walk"). There was no evidence of psychotic thinking; his "out of the blue" comments typically had an underlying clear set of associations. Tom could explain his "getting stuck" in terms of his particular difficulty in responding quickly to unusual situations. He continued to have a markedly eccentric social style and engaged in one-sided conversations about computers and mathematical concepts in a loud, unmodulated voice. His very limited awareness of social conventions was illustrated by his one-sided conversational style, his tendency to belch and pass gas, and his use of graphic expletives with little apparent intention to shock his conversational partner. He perseverated on the subject of girlfriends and his sexual needs. He described approaching unfamiliar girls and answering a question such as "How can I help you" with an explicit sexual request. Psychometric Assessments. The results of the most recent IQ tests are presented in Table 1. There were significant discrepancies between verbal and performance skills, particularly on the testing at 9 years, 8 months. Subsequent gains occurred primarily in the areas of visual-spatial and visualmotor skills and reflect various compensatory strategies he learned to mediate visual tasks by verbal means. For example, in his description of his approach to the WISC-III Block Design test, normally a visual-spatial test, Tom described how he transformed the task by assigning a digit to each of the possible configurations of a cube (0 for white, 1 for red, and 12 for white/red) and then reduced the design into a sequence of digits (e.g., 1-0-0-Yz). Tom had superior scores on verbal reasoning tasks, except for a task involving comprehension of social norms and conventions; although able to describe general social expectations, he was not able to translate this knowledge into appropriate conduct. Tom had significant deficits in visual-motor skills, processing speed, and motor functioning. Adaptive skills (i.e., his ability to meet the demands of everyday life) were assessed by the Vineland Adaptive Behavior Scales (Sparrow et aI., 1984). Standard scores on the Vineland (mean, 100; SD, 15) included 77 in communication, 63 in daily living skills, and 33 in socialization; his adaptive behavior composite standard score was 53. There was a difference of 83 standard points between Tom's overall TABLE 1 IQ Testing

WISC-R" Full Scale IQ VerbalIQ Performance IQ

122 140

90

136 139 127

" Testing was done at age 9 years, 8 months. b Testing was done at age 13 years, 4 months.

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IQ and his adaptive behavior composite, indicating very severe deficits in all areas of functioning and, most prominently, socialization skills. FamilyData. Tom's first-degree relatives had been assessed as part of our research program on AS. His mother, father, and sister had Full Scale IQs in the high-average to superior range. There was great similarity between Tom's intellectual profile and those of his first-degree relatives, particularly his father; there was a 43-point differential between his father's Verbal IQ and Performance IQ (Verbal = 129; Performance = 86). As noted previously, Mr. Z. described himself as "analytical and rational" and had marked difficulties in social interaction. His conversation style was rather rigid, with some disregard to communicative nuances and cues and poor voice and tone modulation. Speech-Communication Evaluation: Wendy D. Marans, M.D.

There was significant variability in Tom's speech-communication competence. His skills in the areas of single-word receptive and expressive vocabulary were excellent but far weaker when he had to cope with nonliteral and social language. His most notable deficit was in figurative language in which he was asked to provide his own interpretation of idiomatic expressions; for example, he simply could not understand what was meant by the phrase "I just can't swallow that," even when he was provided with several contexts and cues. In real situations with peers and adults, some of the nuances and subtleties that would occur in rapid succession in communication would be extremely difficult for him to detect, particularly if he needed to appreciate someone else's point of view. Tom did not modify his language depending on context or cues; his pedantic and long-winded monologues suggested little appreciation of his conversational partner. Although his articulation was accurate, his prosody was significantly deficient; Tom showed a tendency to lengthen vowels in combination with some hypernasality which resulted in a "whining" quality. Thus, while Tom is reported to have had early language skills well within normal limits, his current skills are unusual in a host of ways. Discussion of Testing: Sara Sparrow, Ph.D.

Tom's clinical presentation and formal assessment profile are extreme in many respects. There was a discrepancy of 103 standard score points between his Full Scale IQ (136) and his standard score on adaptive, socialization skills (33). He recalled 11 digits backward and performed remarkable mathematics feats; indeed some of his self-taught mathematical skills were at college levels. On the other hand, he could

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not explain common idioms and his social skills were at extremely low levels. His developmental history and presentation are consistent with the ICD-I0 and DSM-IV definitions ofAS. In addition, he exhibits two features (all-absorbing interests and motor incoordination and clumsiness) which were noted by Asperger (1944) and others but which are not technically required in either the ICD-I0 or DSM-IV definition. In our experience (Klin et al., in press), these are usually observed in "classic" cases. Tom's neuropsychological profile is also consistent with Rourke's (1989) description of nonverbal learning disabilities (NLD). Rourke (1989) has hypothesized that specific deficits involving white matter are involved in the pathogenesis of this condition, which has been associated with various etiologies. Volkmar and Cohen (1991) noted the potential overlap of the NLD and AS. In NLD there is an overreliance on explicit, verbal, analytical, and piecemeal informationprocessing and an underreliance on intuitive, nonverbal, and holistic information-processing. Such a style fosters high performance on circumscribed and logical tasks but sacrifices the understanding of the conceptual underpinnings as well as the broader picture or context of tasks and activities. In the social realm much of the context of social transactions, which are primarily transmitted through nonverbal cues or suprasegmental aspects of speech, are lost because of the exclusive emphasis on the explicit aspects of social transactions (i.e., the literal semantic message). Nonliterallanguage (e.g., figurative language, irony, humor), in which people may say what they do not mean, and mean what they do not say, is a great, sometimes insurmountable, challenge to Tom. From Tom's perspective, his social difficulties and troubles constitute a logical but unfathomable problem. He relates his difficulties to lack of knowledge: for example, he once said that "the thing" he knew the most was "math," while "the thing" he knew the least was "girls." Frustrated by repeated experiences ofsocial failure, and puzzled by concepts such as "affection" and "friendship," he described himself as a "human simulation of an artificial intelligence cognitive being." Tom cannot elaborate on this insight, but his metaphor captures central aspects of his condition: (1) his world is experienced analytically and explicitly, (2) emotional or intuitive information must be reduced to analytical and explicit language to be processed, and (3) despite his estrangement from implicit, social-emotional phenomena, he has a basic interest in others and a wish to be accepted and loved. As noted by Rourke (1989), this combination of features often results in increasing despondence and even depression and may foster a sense of alienation and paranoid ideation. Although he was able to use common affective terms, Tom's actual understanding was highly dissociated from commonly

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understood meanin gs. This conceptual idiosyncrasy may be related to the appare nt pot enti al for individuals like T om to have psychoti c or psycho tic-like phenomena (T anturn, 199 1). Neuroimaging: Richard Bronen, MD .

Father and son had magnetic reson ance imaging (M RI) of the brain , by means of T y-wcigh ted and thr ee-dimension al volume techniques on a G eneral Electr ic Signa 1.5 Tesla mach ine. The father 's sagirtal brain images showed a large V-shaped wedge of missing tissue just superior to the ascending ramu s of the sylvian fissure, at abo ut the level wh ere the mid dle fronta l gyrus norm ally intersects with the precent ral sulcus (Fig. 1). This region of tissue loss is seen bilaterally in the same location bur is somewhat larger on the left. G iven the absence of a history of trauma and lack of evidence of trauma on the MRI , thi s likely represents an area of focal dysm orphology of unkn own or igin. I know of no published reports show ing similar abno rma lities. In oth er respects, the father's two-d imension al images reveal normal brain morphology. T om shows a similar, but not iceably smaller region of focal, bilateral dysmorphology in exactly the same area. Tom's abno rmality, however, is somewha t larger on the right, the reverse of the father's (Fig. 2). In add ition, ther e is decreased tissue in the anterior-infer ior left temporal lobe associated with a pocket of adjacent CSF (Fig. 3). The CSF collection is angulated, sph erical, and witho ut mass effect, suggesting it is not du e to an arachno id cyst. This suggests an atrophic process or a region al neurodevelopm ent al growth failure. The similarity of abnor malities in Mr. Z . and Tom suggests potential familial tra nsmission.

Fig . 1 Sagirral image of the father's brain, showing a triangular region of missing tissue in the dorsolateral aspects of the left fron tal lobe.

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Discussion of MRI and Psychological Testing: Robert Schultz, Ph.D,

Three-d imensional rendering of the fath er's brain clearly showed his neurode velopm enral abn ormality to be at th e intersection of the precentral sulcu s and what would normally be the middle front al gyrus (Fig. 4). The deficit is a recessed area of absent tissue. Moreover, rend ering the images th reedimensiona lly reveals an abnorma lity that could no t be appreciated on the two-dimension al images: bot h right and left fronta l lobes show an abe rrant pattern of gyri and sulci. Normally, the frontal lobe is characterized by th ree prom inent hor izonta l gyri (th e superior, middle, and inferior frontal gyri) running in parallel from anter ior to post erior. Whil e the father's superior frontal gyrus is evident and norm al in appe arance bilaterally, th e horizontal orient ation of th e midd le frontal gyri canno t be clearly identified in either hemisphere. Instead we see a prominent vertical orientat ion of gyri in this region such that two gyri proceed from the inferior-most aspect of the frontal orbi tal region and inte rsect in a perpendicular fashion with the superior front al gyrus. We speculate that the aberrant pattern of surface mor pho logy is related to the adjacent region of focal decreased tissue and stems from an abno rmal prenatal developmental process. Because of slight movement artifacts, clear three-dimensional rend ering of T om's brain was not possible. I was, however, able to reslice the image by computer methods in a coronal plane to evaluate the left tem poral lobe abn ormality. This is evident as a large region of missing tissue. These images also revealed asymm etry of the lateral ventricles, with the right side appearing com pressed relative to the left. Any single case report mu st be interpreted with caution, yet it is of interest that Tom 's neuropsychological deficits are sensible in light of these brain abnormalities and should

Fig. 2 Sagiua l image of the son's brain, showing a similar but smaller abnormality in exactly the same locatio n as the father's.

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Fig. 3 Axial view of the son's brain. The arrow points to the anteriormesial aspect of the left temporal lobe, where a pocket of C:SF fills a region of decreased brain tissue.

be interpreted within the context of other studies of individuals with autism, AS, and similar disorders (e.g., Piven et al., 1990). As described earlier, Tom's psychological testing revealed much higher Verbal IQ than Performance IQ. Generally speaking, the right hemisphere is associated with skills underlying success in Performance IQ subtests, while the left is more oriented toward language and verbal skills reflected in Verbal IQ.

Fig. 4 Three-dimensional reconstruction of the father's brain images. The circle encompasses the region of missing tissue first seen in two dimensions in Figure 1.

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Commensurate with his greater nonverbal difficulties, Tom's frontal lobe abnormalities were more prominent on the right than left side. Moreover, volumetric assessment of the two cerebral hemispheres found the left to be somewhat larger overall than the right. In a study published several years ago, we (Willerman et al., 1992) noted that a larger left than right hemisphere predicted a higher Verbal IQ than Performance IQ in males. The right hemisphere is also more intimately involved in regulating language prosody (both production and reception) and pragmatics than is the left hemisphere (Kolb and Whishaw, 1990), two areas in which Tom performed quite poorly. However, his temporal lobe findings were opposite of what we expected. His test results indicated velY poor nonverbal memory and good verbal memory, yet his MRI showed abnormalities in his mesial left temporal lobe, an area which, when lesioned in adulthood, often results in verbal memory deficits. The frontal lobe findings, on the other hand, may clarify Tom's motor difficulties and problems with conceptual flexibility. The morphological abnormality was at the juncture of the primary motor strip, premotor area, and dorsolateral convexity, thus possibly affecting the functions mediated by each of these brain regions. The dorsolateral prefrontal cortex is known to be involved in the executive functions ofworking memory processes and to mitigate against interference effects (Goldman-Rakic, 1987). Discussion: Donald J. Cohen, M.D.

The issue of inclusion of "new" categories in DSM-IV was complex, and the inclusion of AS as an official category was controversial. As Dr. Volkmar has noted, on the one hand, AS has been viewed as a variant of, if not actually an alternative term for, higher-functioning autism. On the other hand, the continuities of AS with other disorders such as schizoid personality disorder (e.g., Wolff and Chick, 1980), semantic-pragmatic disorder (Bishop, 1989), and NLD (Rourke, 1989) highlight the importance of this condition as a "bridge" from the PDDs to other conditions. Additional data, e.g., of the kind presented in this case, are particularly important to clarify continuities and discontinuities (KEn et al., in press; Ozonoff et al., 1991). More research on this conditio'n and its association with specific neuropsychological and neuropsychiatric features and with neurobiological findings will help clarity these issues; such research should emphasize aspects of both internal and external validity and attempt to avoid some of the circularity that has marked some of the previous work in this area. Apart from the important, practical, clinical perspectives, the possibility of correlating specific patterns of clinical, neuropsychological, and morphological findings, as in this case, provides a new theoretical approach to studying brain-

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behavior relationships psychopathology.

In

the emergence of developmental

Response: Dr. Volkmar

The issues of differential diagnosis of AS and autism are complex, not least of all because the official definitions are quite recent and will likely need to be further refined if, as I suspect, available evidence continues to support the differentiation of the conditions. As presently defined in DSM-IV(American Psychiatric Association, 1994), the major point of differentiation has to do with comparatively good early language skills in AS. This is not typically true in autism; there may be confusion ofthe conditions, particularly if reliable historical information is absent; in such cases the diagnosis of autism should take precedence. It is important to note that even if the early language development in AS is normal, subsequent communication development is not necessarily normal. As was true of Tom, older children and adults with AS often exhibit marked difficulties with figurative language, conversational skills, and other pragmatic abilities even though other aspects of language may be preserved. In addition it should be noted that in our experience the criteria from both ICD-10 and DSM-IV might well be improved, i.e., made more stringent, since it appears that both motor clumsiness and circumscribed interests are usually observed in AS. Ultimately, the usefulness of this diagnostic category must be established on the basis of empirical research. At present the major reasons for including this category rest both on its differentiation from autism and the apparently higher frequency of transmission of this condition within families.

REFERENCES American Psychiatric Association (1994), Diagnostic and Statistical Manual ofMental Disorders, 4th edition (DSM-IV). Washington, DC: American Psychiatric Association

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