sions. Unilateral damage produced a brief, transient shift of the eyes to the ipsilateral side. On recovery, removal of the second frontal eye field resulted in a longer-lasting deviation of the eyes to the newly lesioned hemisphere. There is evidence that each fron- tal eye field may be involved in conjugate, horizontal eye movements, not only in the contralateral, but also in the ipsilateral direction. Electrical stimulation of the frontal eye field in the alert monkey produces mainly contralateral but also ipsilateral eye movements [9]. There are focal increases in regional cerebral blood flow in the frontal eye field during contralateral as well as ipsilateral horizontal eye movements in human sub- jects, indicating neuronal activation of this region [b]. Eye movements recover even after unilateral hemi- spherectomy [lo], and CED does not occur with slowly progressive destructive or degenerative lesions of the frontal area. Taken together, the data suggest that disappearance of CED after acute stroke involving the frontal lobes and their connections depends on the integrity of the contralateral frontal eye field in patients with acute hemispheric stroke.

Supported in part by a grant donated by the Blaustein family for cerebrovascular research.

References 1.

2.

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Daroff RB, Troost BT: Supranuclear disorders of eye move- ments. In Glaser JS (ed): Neuro-ophthalmology. Hagerstown, MD, Harper & Row, 1978, pp 201-218 De Renzi E, Colombo A, Faglioni P, Gibertoni M: Conjugate gaze paresis in stroke patients with unilateral damage: an unex- pected instance of hemispheric asymmetry. Arch Neurol

Gay A, Newman N, Keltnerj, Stroud M: Eye Movement Disor- ders. St Louis, Mosby, 1974, p 20 Hoyt WF, Frisen L Supranuclear ocular motor control: some clinical considerations- 1974. In Lennerstrand G, Bach-Y-Rita P (eds): Basic Mechanisms of Ocular Motility and Their Clinical Implications. Wennergren International Symposium Series, Vol 24. Oxford, England, Pergamon, 1975, pp 379-392 Latto R, Cowey A: Fivation changes after frontal eye field lesions in monkeys. Brain Res 30:25-36, 1971 Melamed E, h s e n B: Cortical activation pattern during saccadic eye movements in humans: localization by focal cerebral blood flow increases. Ann Neurol 5:79-88, 1979 Pasik P, Pasik T: Oculomotor functions in monkeys with lesions of the cerebrum and the superior colliculi. In Bender MB (ed): The Oculomotor System. New York, Harper & Row, 1978, pp

Pedersen RA, Troost BT: Abnormalities of gaze in cerebrovas- cular disease. Stroke 12:251-254, 1981 Robinson DA, Fuchs AE: Eye movements evoked by stimula- tion of frontal eye fields. J Neurophysiol 32:637-648, 1969 Troost BT, Weber RB, Daroff RB: Hemispheric control of eye movements. I. Quantitative analysis of refixation saccades in a hemispherectomized patient. Arch Neurol 27:44 1-448, 1972

39~482-486, 1982

201-218

Genetic Testing in Huntington’s

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NOTES AND LETTERS

Disease William C. Koller, MD, PhD, and Joyce Davenport, MSW

The presymptomatic detection of gene carriers of Hunting- ton’s disease has not been previously possible 151. The recent discovery of a genetic marker linked to the Huntington gene has made it likely that a reliable predictive test or even gene identification itself will soon be available {4]. Controversy exists regarding the value and ethics of such testing, however {2,3, 111. To assess the views of persons at risk, we surveyed 7 5 individuals with an affected parent, asking whether they would take a test to identify the presence of the Hunting- ton’s gene. O n the questionnaire they could respond yes, no, or undecided, and state the reason for their choice. Of the 75, 61 (81%) indicated a desire to take the test when it became available. Reasons for their willingness included elimination of uncertainty about the future and the ability to plan for it intelligently, to decide whether to have children, and to know if they could have passed the gene on to their children. Nine (1 2%) indicated that they would not take the test, stating that they did not want to know a future that they perceived as

hopeless. Five (7%) were undecided. In another survey of an American population, 77% (307 of 339) indicated willing- ness to take a predictive test 181. In the United Kingdom 80% (80 of 100) and in Wales 56% (51 of 91) of individuals surveyed wished to take such a test El, 12). In an Australian study, 84% of at-risk subjects were found to have a positive attitude toward a predictive test [lo].

The results of a reliable genetic test would produce two groups: those who have escaped the disease and those who possess the gene. It has been suggested that the latter group will be deprived of all hope and be prone to despondency and possible suicide {9]. Several authors have stated, therefore, that predictive testing should not be offered to anyone until effective treatment or a cure becomes available [b, 91. This view is centered on the presumed need to protect individuals from the knowledge that they will develop an incurable dis- ease. Hope is, however, far from totally lost. Symptoms may not occur for many years, and useful lives are possible for some time even after the onset of symptoms. The opportu- nity to cope, prepare, and plan appears for many individuals more desirable than the burden of uncertainty. Treatment (neuroleptics) already exists for control of some symptoms. Laypersons also express the realistic hope that future research advances will lead to suppression of the illness within their lifetimes. Currently there are no data that indicate any poten-

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tial harm from predictive testing. As one of our patients stated, “The medical profession should not be making the decision about the test; those at risk have a right to know.” A minority of the patients themselves feel that they would han- dle poorly the fact that they have the gene and have indicated they would not take the test. The vast majority of those at risk, however, both in our survey regarding genetic testing and in past surveys regarding a theoretical predictive test, wish to know their gene status. It has been further suggested that the failure of gene carriers to procreate would quickly result in elimination of Huntington’s disease and the suffer- ing it causes 171.

It is important that predictive testing, when available, be accomplished in a carefully supervised manner, with social workers, psychologists, and neurologists familiar with Hun- tington’s disease providing counsel and support to those undergoing testing, both before and after genetic determina- tion. Also necessary is the collection of data regarding the psychological implications for tested carriers and the possible determinants of subsequent constructive and destructive be- havior. It is our belief that it is the task and the challenge of the medical profession to administer genetic testing in a re- sponsible and compassionate manner.

Department of Neuroloa LoyoIa Univwsity Stritch School of Medicine 21 60 S First Ave Maywood, IL 60153

References 1. Barette J, Marsden CD: Attitudes of families to some aspects of

Huntington’s chorea. Psycho1 Med 9327-336, 1979 2. Bates M: Ethics of provocative test for Huntington’s disease. N

Engl J Med 304:175-176, 1981 3. Brackenridge CJ: Ethical aspects of plans to combat Hunting-

ton’s disease. J Med Ethics 7:24-27, 1981 4. Gusella JF, Wexler NS, Connedy PM, et al: A polymorphic

DNA marker genetically linked to Huntington’s disease. Nature

5 . Klawans HL, Goetz CG, Perlik S: Presymptomatic and early de- tection of Huntington’s disease. Ann Neurol 8:343-349, 1980

6. Marsden CD: Predictive testing in Huntington’s disease. Ann Neurol 10:202-203, 1983

7. Robertson M: Towards a medical eugenics. Br MedJ 288:429- 430, 1984

8. Stern R, Eldridge R: Attitudes of patients and their relatives to Huntington’s disease. J Med Genet 12:217-223, 1975

9. Stevens DL Tests for Huntington’s chorea. N Engl J Med

10. Teltscher B, Polgar S: Objective knowledge about Huntington’s disease and attitudes towards predictive test of persons at risk. J Med Genet 18:31-39, 1981

11. Thomas S : Ethics of a predictive test for Huntington’s chorea. Br Med J 284:1383-1389, 1982

12. Tyler A, Harper PS: Attitudes of subjects at risk and their rela- tives towards genetic counselling in Huntington’s chorea. J Med Genet 20:179-188, 1983

306:234-238, 1983

285 :4 13-4 14, 197 1

Editorial Comment Joseph B. Martin, MD, PhD

The identification of a restriction fragment length polymor- phism (RFLP) mapped to chromosome 4 and linked to the

Huntington’s disease (HD) gene represents an unprece- dented breakthrough, not only in HD research, but also in the use of recombinant DNA technology in the investigation of inherited diseases. Genes that code for inherited diseases with identified gene products (sickle cell anemia and beta thalassemia) have been isolated in the past using recombinant DNA technology. The methodology for isolating genes that code for well-characterized proteins, such as insulin, globin, and immunoglobulins, is well established. The discovery of the localization of an RFLP linked to the H D gene, however, is the first use of this technology to localize a gene without prior knowledge of the gene location or product. This ap- proach is applicable to any inherited disease, providing an entry to the study of a variety of autosomal dominant disor- ders. For HD at the present time neither prenatal nor presymp-

tomatic testing of at-risk persons is available. Testing of this kind will probably begin on a limited basis in 1985. It cannot yet be assumed that all cases of HD are caused by the gene located on chromosome 4. A number of additional large families with HD are currently being tested for linkage. In addition, the frequency of recombination between the link- age marker and the HD gene has not been fully determined. The frequency of false positive and false negative recognition of gene carriers will depend on how close the linked marker is to the HD gene. The closer the linkage, the less the likeli- hood of recombination and the greater the accuracy of the test. The current test under the best circumstances cannot provide more than a 95% accuracy.

In order to understand better the difficulties in developing a presymptomatic test for HD, it must be remembered that the gene itself is not being tested but, rather, a RFLP marker close to the gene. In different families the marker linked to the H D gene occurs in different forms, and thus the variety of the linked polymorphism must be identified in each family of an at-risk person who wishes to be tested. To accomplish this identification, several members of the family, including those already diagnosed with HD, those old enough to be probable noncarriers, and the unaffected parents of the at- risk person, are needed. Those at-risk persons with no living diagnosed relative will not be able to be tested with the current methodology unless tissues of diagnosed relatives are saved in brain tissue banks. Furthermore, some at-risk per- sons with living HD-affected relatives will not be able to learn their HD gene status if their affected parent happens to be homozygous for the linked marker.

I agree almost totally with the comments expressed by Koller and Davenport. It is remarkable how consistent the results of various surveys of at-risk individuals are, including a recent one carried out in our own New England population, in indicating that about 75% of individuals wish to know their fate. Although presymptomatic testing of other condi- tions is possible, the potential for unpredictable responses of at-risk patients with HD may be unique. These patients know the frequency with which psychiatric symptoms precede the “neurological” disorder, and the psychological pressure pro- duced by knowing that the disease will occur may be substan- tially more than we would predict. The patients’ right to know is an important issue, and when the linkage test is fully validated in a larger number of pedigrees and made more informative by the development of additional probes closer

512 Annals of Neurology Vol 16 No 4 October 1984