Arthur K. Shapiro

Gilles de la Tourette's syndrome Clinical, genetic, psychologic, and biochemical aspects in 21 selected families

Eighty-one patients and relatives with Tourettes syndrome, members of 21 selected families, participated in a 1-day clinic. In 12 of the 13 Jewish families and six of the eight non-Jewish families, there were multiple members with motor and vocal tics by observation or history. Males predominated among those with persistent symptoms, but among those with spontaneous clearing, females predominated. Twelve propositi had troublesome sexual and aggressive impulses, differing only quantitatively from normal. No evidence of abnormality was found in plasma dopamine beta hydroxylase, or norepinephrine levels.

Neurological features of Gilles de la Tourette's syndrome

Clinical neurological examinations of 22 patients with Gilles de la Tourettes syndrome and written reports of examinations of seven other patients are reported. Half the personally examined patients had minor motor asymmetries in addition to the typical motor and vocal tics found in all the patients. Thirty-six per cent of patients were left handed or ambidextrous. Electroencephalograms performed on 17 of the 22 patients showed non-specific abnormalities in 12 of them. These findings suggest that a neurological disorder underlies Tourettes syndrome, but they do not clarify its nature.

THE SYMPTOMATOLOGY AND DIAGNOSIS OF GILLES DE LA TOURETTE'S SYNDROME

The focus of this paper is the symptomatology and diagnosis of Gilles de la Tourettes syndrome, the result of a study of the data collected on 34 patients, including detailed psychiatric, psychological, neurological, electroencephalographic, demographic, and treatment evaluation. Based on our experience with these patients and a review of the literature, we concluded that the diagnosis of Gilles de la Tourettes syndrome is difficult to make. In this paper, therefore, we propose: (1) to evaluate the symptomatology and establish minimal criteria for the diagnosis of this syndrome; and (2) to review the data collected, comparing them with the findings of other investigators.

Semantics of the placebo

SummaryWith increased interest in the placebo effect and clinical methodology, definitions of the placebo have proliferated. But there is little agreement among lexicographers, historians, clinicians, and researchers about how to define this word.Derivations of the wordplacebo from the Hebrew and Latin and its use in the Bible and literature were reviewed. Historical inaccuracies in classical references to the placebos origin, history, and development were corrected. An explanation was given for the introduction of the word in 1785, and for the changes in definition that have appeared since that time. Definitions of the placebo and placebo effect, based on historic considerations and heuristic principles, were then proposed.

Tourette's syndrome: summary of data on 34 patients.

&NA; A review of the data collected on 34 patients with Gilles de la Tourettes syndrome was presented. The data summarized the demography, birth, developmental, and family histories of these patients. The development and characteristics of the symptomatology were described. Psychopathological theories suggested in the literature as etiologically related to Tourettes syndrome were not confirmed. Evidence was presented in support of the hypothesis that the etiology of Tourettes syndrome is an organic impairment of the central nervous system. The difficulties in diagnosis were reviewed and a description of the syndrome was provided. The treatment history with haloperidol of these patients was outlined. Early diagnosis of Tourettes syndrome is important now that an effective treatment is available.

Birth, developmental, and family histories and demographic information in Tourette's syndrome.

Demographic information, including sexual, religious, social and ethnic background, and marital status, as well as birth, developmental, and family history, was collected for 34 patients with Gilles de la Tourettes syndrome, and compared with the findings in six studies and four reviews. Males outnumbered females at all ages in a ratio of three or four to one. Sixty-seven per cent had an East European Jewish background. More females were married than males. There was no relationship between Tourettes syndrome and mothers age at birth, history of abortions, birth history, birth order, family history of tics and mental illness, and social class. In 60 per cent of the cases, one of the parents had paranoid or dominant characteristics, higher than might be expected. Childhood developmental abnormalities were found in 51.8 per cent of the patients and 35.3 per cent were left-handed. These findings suggested a relationship between Tourettes syndrome and early central nervous system difficulty. The median age of onset was 6.5 years with a range of 3 to 13 years, duration of illness was 12.6 years with a range of 3.5 to 54 years, and duration between onset of symptoms and the diagnosis of Tourettes syndrome was 9.0 years with a range of 0.2 to 54 years. Early and correct diagnosis of Tourettes syndrome is important to minimize the harmful effects on patients of delayed chemotherapy which is now available.

Study of the placebo effect with a placebo test

Summary This paper briefly reviewed several methodological problems in studies of the placebo effect. The importance of finding appropriate measures of placebo effect was emphasized. This led to an attempt to develop a more valid and reliable test of placebo reactivity. Use of the placebo test led to the following tentative conclusions: Inferences made about placebo effects vary with the method of scoring placebo reactions. The placebo effect consists of a group of nonreactors to the placebo, and a second group of reactors but without regard to positive or negative direction. The reactive group is subdivided into predominantly positive or negative groups. Thus, comparing positive reactors with a combined group of nonreactors and negative reactors obscures important differences among groups. Patients with positive reactions to placebo tend to improve more rapidly and have a better prognosis than patients with neutral and negative reactions. Patients with absent and negative responses may respond to treatment eveually but not as predictably as positive reactors. Other confirmed predictions were that positive and negative placebo reactions would be unrelated to older age, lower intelligence, authoritarianism, duration and severity of illness, and diagnosis, and that placebo reaction would be related to anxiety and depression. The placebo test may combine the best features of a simple, standardized, quantitative, and reliable laboratory test of suggestibility with the clinical relevance and validity of the placebo effect. These conclusions are qualified by the limitations of the study, particularly the small sample. This paper should be considered a report of preliminary findings which should be investigated further.

Eye-blink Rate in Tourette's Syndrome

Gilles de la Tourettes syndrome is a hyperkinetic movement disorder in which an etiological role for dopaminergic hyperactivity has been proposed. Blink rate, a putative correlate of central dopamine activity, is commonly held to be elevated in Tourettes syndrome, a finding that would be consistent with the “dopamine” hypothesis of this disorder. In 19 patients who had Tourettes syndrome, however, blink rates during placebo treatment were identical with those of 49 index controls during reading and quiet sitting. Blink rate did correlate, however, with both the number and severity of tics. Pimozide treatment did not reduce blinking in the patients. It should be noted that nine of the patients were adolescents for whom there were not adequate age-matched controls, a fact which could obscure a blink rate elevation in this group. Insofar as blink rate is a putative correlate of central dopamine activity, these results are not consistent with elevated brain dopamine activity in adult patients who have Tourettes syndrome.

Differential Diagnosis of Gilles de la Tourette's Syndrome.

Gilles de la Tourettes syndrome, a rare and fascinating movement disorder, has often been poorly understood and misdiagnosed by physicians. In reviewing the literature it becomes apparent that much of the diagnostic confusion may be attributed to the fact that Gilles de la Tourette himself failed to differentiate the syndrome which bears his name from other obscure disorders described in his time. Also, Tourettes original paper has been frequently misquoted. On the basis of our experience with 34 patients who have been intensively studied over a period of 6 years, diagnostic criteria for the diagnosis of Tourettes syndrome have been set forth. The symptoms have been found, to start between the ages of 2 and 13, usually in the form of simple involuntary tic-like movements. Involuntary noises, often described as barks, grunts, or hisses, were also common initial symptoms. In the course of time the symptoms insidiously change. They will wax and wane in intensity and new symptoms will replace old ones. Movements usually progress from simple to multiple and may often become complicated, appearing purposeful, but remaining entirely involuntary. Although sounds or words appear eventually in all patients, coprolalia is not a necessary component of the syndrome and was present in only slightly more than half of our patients. Contrary to many statements in the literature there is no mental deterioration. In order to aid the physician in diagnosing this rare syndrome, a review of other movement disorders which may enter into the differential diagnosis has been undertaken. The basic characteristics, associated symptoms and findings, courses without treatment, and types of movements seen in these various disorders are discussed and also summarized in a table. It is hoped that this will enable physicians to diagnose the syndrome earlier in its course and more frequently since effective treatment with haloperidol is now possible.

Study of the Placebo Effect With a Self-administered Placebo Test

Abstract An attempt was made to develop a self-administered test of placebo reactivity that combined the reliability of a test of suggestibility with the clinical validity of reaction to the placebo effect. Response to the Placebo Test was determined by a patients response to a placebo tablet, which was taken by the patient at home for the ostensible purpose of determining which medicine would be most helpful to him. The Placebo Test and other information were collected after the patients initial intake evaluation at a psychiatric clinic. A series of independent variables were related to the Placebo Test as dependent variables, and an attempt was made to predict clinical course for patients in psychiatric treatment. Although the Placebo Test had high internal-consistency reliability of measurement, it may have had low validity as a test of placebo-proneness, as evidenced by the difficulty of selecting relevant parameters for measurement of the placebo effect. Depending on the method of measurement, 32 to 36 patients had positive reactions, 36 to 49 had neutral reactions, and 14 to 30 had negative reactions. Thirty-eight patients had side effects from the placebo, and 15 refused to take the test. In general, the results obtained varied with the method of scoring the Placebo Test, except for the major finding that negative placebo reactors were clearly differentiated from positive reactors and nonreactors, who were not significantly different from one another. The conclusion, now supported by two studies, is that analysis of placebo studies requires that positive reactors not be compared to a pooled group of negative reactors and nonreactors. In addition, analysis should include patients who refuse to take the placebo. The relationship between patient improvement and the likability measures is the strongest relationship among variables and improvement, and it warrants further study.