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intellectual functioning as aresult of fenfluramine treatment, nor were there any meaningful changes in clinical ratings of primary autistic disturbances.
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available on the market. Uncontrolled experimenting may have quite large proportions. The problem is that the drug obviously does not have any noticeable positive effects on the behavior of autistic children. According to August, Raz, and Baird (1987), no significant improvements were observed in intellectual functioning as aresult of fenfluramine treatment, nor were there any meaningful changes in clinical ratings of primary autistic disturbances. In an uncontrolled setting the apparent lack of effects might lead the parents to increase the dosage in the hope of a noticeable response. This is certain to lead to complications, if not irreversible brain damage. According to Pranzatelli and Snodgrass (1985), convulsions and coma have been reported in humans with doses as low as 5 mg/kg. The neurochemical effects in humans are largely unstudied. In animals the threshold for midbrain raphe injury is 1.5 mg/kg, which is the lowest dosage (2 tablets per day for a child of 25-30 kg) used in the experiments. We urge all parents to refrain from experiments with fenfluramine. All autistic children and adults who have been subjected to the drug must be monitored for adverse short- and long-range effects. Great caution should be taken to minimize withdrawal effects. In the future, greater restraints should be shown in promoting easily available drugs for experimental use. Bernt and Marianne Sj6holm (Parents o f an autistic child) Ruutikellarintie 2 A 3, SF-02600 Espoo, Finland

REFERENCES

August, G. J., Raz, M., & Baird, T. D. (1987). Fenfluramineresponsein high and low functioning autistic children. Journal of the American Academy of Child and Adolescent Psychiatry, 26, 342-346. Pranzatelli, M. R., & Snodgrass, S. R. (1985). Fenfluraminetherapy for autism. Journal of Autism and Developmental Disorders, 15, 439-441.

LACK OF SIMILAR FINDINGS MAY BE DUE TO UNDERUTILIZATION OF MRI TECHNOLOGY The recent report by Gaffney and Tsai (1987) presented data from Magnetic Resonance Imaging (MRI) of 14 subjects with autism. They conclude that their "search for a single pathognomonic parenchymal brain lesion with MRI in autism was not fruitful." I suggest that their lack of similar findings across more subjects may be due to underutilization of the data that MRI can provide.

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In their study, MRI scans were clinically evaltiated by neuroradiologists. Although this is a fine first step for locating visually apparent or typical types of brain abnormalities, it is a very gross level of analysis and has important limitations as a research technique. Visual inspection relies on a subjectively defined range of normal that, without reliability data, cannot be assumed to be consistent across examiners. Likewise, the conclusion that "a significant number of the patients who were referred for scanning have brain abnormalities" begs the basic research question, significant compared with what? Normally functioning adults can show brain abnormalities of no apparent behavioral importance. The reader cannot evaluate these data without an idea of "normal" prevalence rates for these features. Gaffney and Tsal (1987) ruled out evaluator bias on the basis of a lack of previous radiological findings associated with autism. Although previous knowledge may bias the examiner towards overreporting, the opposite effect is possible when no direction is used. If an examiner does not have a predefined feature to look for, and idea of where it may be found, that feature may be underidentified or missed completely. The following investigation illustrates how a data-based approach can focus observations on appropriate sites. Following reports that described abnormalities in the neocerebellar cortex of subjects with autism (Bauman & Kemper, 1985; Courchesne, Hesselink, Jernigan, & Yeung-Courchesne, 1987; Ritvo et al., 1986; Williams, Hauser, Purpura, Delong, & Swisher, 1980), Courchesne and his colleagues developed an area measurement for MRI to reliably quantify differences in the neocerebeUum of autistic and normal subjects. Like Gaffney and Tsai (1987), Courchesne (in press) studied subjects with autism who showed normal performance IQs. Compared with normal controls, 14 of 18 subjects with autism presented with abnormally small vermal lobules VI and VII relative to their typically normal (in size) anterior cerebellar vermis. When contrasted with the more subjective assessments of Gaffney and Tsai, these findings illustrate that different conclusions may be reached with different uses of the same research tool. To develop and use quantitative measures (i.e., lengths, areas, volumes), attention must be given to the scan parameters, slice placement, and slice tilt to obtain accurate and reliable measures of brain areas. Slice thickness impacts the structures that can be delineated. For example, the 10 mm-slice thickness used by Gaffney and Tsai would not be optimal for viewing the cerebellar vermis which is often less then 10 mm thick. Quantitative measures allow for a statistically based standard of normal. From this, investigators are able to describe differences that are beyond a range reasonably explained by individual variability or measurement error. The rationale for examining a particular region and the methodology

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used must be evaluated in regards to how closely they follow the purpose o f the study. I thank Eric Courchesne for providing me with resources and guidance in m y introduction to the use o f M R I with developmental disorders. I also thank Linda Swisher for her insightful discussion during the preparation o f this letter. Elena Plante Child Language Laboratory, The University o f Arizona

REFERENCES Bauman, M., & Kemper, T. (1985). Histoanatomic observations of the brain in early infantile autism. Neurology, 35, 866-874. Courchesne, E. (in press). Cerebellar changes in autism. In J. Swann& A. Messer (Eds.), DISorders of the developingnervoussystem: Changing viewson their origins, diagnosesand treatments. New York: Alan R. Liss. Courchesne, E., Hesselink, J. R., Jernigan, T. L., & Yeung-Courchesne, R. (1987). Abnormal neuroanatomy in a nonretarded person with autism. Archives of Neurology, 44, 335-341. Gaffney, G. R., & Tsai, L. Y. (1987). Brief report: Magnetic resonance imaging of high level autism. Journal of Autism and DevelopmentalDisorders, 17, 433-438. Ritvo, E. R., Freeman, B. J., Seheibel, A. B., Duong, T., Robinson, H., Guthrie, D., & Ritvo, A. (1986). Lower purkinje cell counts in the cerebella of four autistic subjects: Initial findings of the UCLA-NSAC autopsy research report. American Journal of Psychiatry, 143, 862-866. Williams, R. S., Hauser, S. L., Purpura, D. P., DeLong, R., & Swisher, C. N. (1980). Autism and mental retardation: Neuropathologicstudies performed in four retarded persons with autistic behavior. Archives of Neurology, 37, 749-753.

R E S P O N S E T O " L A C K OF S I M I L A R F I N D I N G S M A Y BE D U E T O U N D E R U T I L I Z A T I O N OF MRI T E C H N O L O G Y " We agree with Ms. Plante that "quantitative measures" should be applied to M R I studies. In our brief report we stated that we were pursuing quantitative planimetedc analyses o f M R I in this group o f high-level autistic patients (Gaffney & Tsai, 1987). A series o f papers with these results will be published in the near future (Gaffney, K u p e r m a n , Tsai, & Minchin, in press-a, in press-b). Our quantitative analyses o f the M R I scans indicated larger 4th ventricular and smaller cerebellar, pontine, and brainstem measures in the autistic group as compared to those of the control group. However, the variances were large, suggesting that this g r o u p o f children with autism p r o b a b l y is not homogeneous with regard to neuroanatomical substrate.

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The point o f our brief report (Gaffney & Tsai, 1987) was that, when using clinical, visual examination o f M R I , a single, obvious, p a t h o g n o m o n ic lesion was not identified in the syndrome. Apparently neuroanatomic alteration in autism is subtle, requiring sensitive quantitative methods to delineate.

Gary R. Gaffney and Luke Y. Tsai Division o f Child Psychiatry, University o f Kansas Medical Center, Kansas City REFERENCES Gaffney, G. R., Kuperman, S., Tsai, L. Y., & Minchin, S. (in press-a). Midsagittal magnetic resonance imaging of autism. British Journal of Psychiatry. Gaffney, G. R., Kuperman, S., Tsai, L. Y., & Minchin, S. (in press-b). Morphological evidence for brainstem involvement in infantile autism. BiologicalPsychiatry. Gaffney, G. R., & Tsai, L. Y. (1987). Brief report: Magnetic resonance imaging of higher-level autism. Journal of A utism and DevelopmentalDisorders,. 17, 433-438.