Self-Injurious Behavior In Lesch-Nyhan Syndrome (1985)

©1985, 2013 by Dallas Denny

Source: Denny, Dallas. (1985). Self-injurious behavior in Lesch-Nyhan Syndrome: A review of the efficacy of various treatment strategies. Paper for Dr. Jim Fox, George Peabody College of Vanderbilt University.

 

 

 

Self-Injurious Behavior In Lesch-Nyhan Syndrome

A Review of the Efficacy of Various Treatment Strategies 

By Dallas Denny 

For Dr. Jim Fox

Special Education 3400

 Fall, 1985

 

Abstract

Lesch-Nyhan Syndrome is a metabolic disorder which results in hyperuricemia and central nervous system manifestations of reduced intellectual functioning, spastic cerebral palsy, choreoathetosis, and self-injurious behavior. Although Lesch-Nyhan Syndrome is quite rare, it has become well known to physicians and psychologists and receives obligatory mention in most reviews of self-injurious behavior. The disorder is genetically transmitted as a sex-linked autosomal recessive character. Lesch-Nyhan Syndrome is of particular interest because of the clear-cut relationship between a deficiency of a single enzyme and a pathological behavior (self-injurious behavior). The self-injurious behavior of individuals with Lesch-Nyhan Syndrome is very severe. It usually manifests itself as biting of the fingers, lips, and/or tongue, with resulting tissue loss. The traditional methods of managing these behaviors are mechanical restraints or extraction of teeth. Various chemical and behavioral interventions have been attempted. To date, no clearly superior chemical treatment has emerged for individuals with Lesch-Nyhan Syndrome. Differential reinforcement of incompatible behavior (DRI) has produced lasting decreases of self-injurious behavior which generalize across settings.

Lesch-Nyhan Syndrome (L-N) is a rare metabolic disorder which results in hyperuricemia and central nervous system manifestations of reduced intellectual functioning, choreoathetosis, spastic cerebral palsy, and self-injurious behavior (SIB). Its frequency of occurrence has been estimated as 1 in 380,000 births (Crawhall, Henderson, & Kelley, 1972). The disorder is caused by a defect in purine metabolism which has been traced to the almost complete lack of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) (Lloyd, Hornykiewicz, Davidson, Shannak, Farley, Goldstein, Shibuya, Kelley, & Fox, 1981; Seegmiller, Rosenbloom, & Kelley, 1967).

Individuals with L-N have an elevated rate of uric acid production, with urinary stones and gouty arthritis (Nyhan, 1973; Watts, McKeran, Brown, Andrews, & Griffiths, 1974). Primary diagnosis is by analysis of the blood and by autoradiography (Jenkins, 1971), although after the first several years, the distinctive form of self-injurious behavior which is characteristic of the disorder can aid in diagnosis (Christie, et al. 1982; Nyhan, Johnson, Kaufman, & Jones, 1980). The presence of “orange sand” in diapers is common, and can be used as a screening tool (Christie, et al. 1982; Hoefnagel, Andrew, Mireault, & Berndt, 1965). Infants at risk for L-N can be identified by assessing the uric acid:creatine ratio of blood samples (Crawhall, Henderson & Kelley, 1972). Screening for Lesch-Nyhan Syndrome has become routine in Quebec (Mclrtnes, Lamm, Claw, & Scriver, 1972).

Prenatal diagnosis via amniocentesis is possible; this makes possible decisions regarding early treatment or interruption of pregnancy (Crawhall, Henderson & Kelley, 1972; Fernald, 1976; Friedmann, 1971; Nyhan, 1973). Since L-N is genetically transmitted as a sex-linked autosomal recessive character (Seegmiller, Rosenbloom & Kelley, 1967), families who have given birth to an individual with L-N or who have a history of gout with resulting self-injurious behavior should receive genetic counseling.

Lesch-Nyhan Syndrome was first formally described by Lesch & Nyhan (1964), who noted that 15 cases had been described in the literature since 1823. Shortly after Lesch & Nyhan’s initial description of the disorder in two young brothers, other cases were reported (Hoefnagel, et al. 1965; Sass, Itabashi, & Dexter, 1965; Dodge, 1966; Peed, 1966; Michener, 1967; Partington & Hennen, 1976). All persons reported affected to date have been male (Christie, et al. 1982). Seegmiller, Rosenbloom, & Kelley (1967) reported that L-N is a sex-linked autosomal recessive genetic defect which results in an almost complete lack of hypoxanthine-guanine phosphor ibosyltransferase (HGPRT).

L-N has excited considerable interest in the medical community and with psychologists, presumably because of the well-established link between the lack of a particular enzyme and the presence of pathological self-injurious behavior (Fernald, 1976), which occurs in all cases of L-N. The literature includes a number of clinical descriptions of L-N, an autopsy report, genetic and metabolic studies of the HGPPT deficiency, and attempts to manage the severe self-injurious behavior which characterizes L-N by mechanical, chemical, dietary, and behavioral means. L-N is now mentioned in most general reviews of self-injurious behavior (cf Putnam & Stein, 1985) and in textbooks (cf Kaufman, 1985). This paper will describe L-N and will review the various methods used to control the SIB associated with the disorder.

 

Physical and Behavioral Characteristics

Infants with L-N are typically born after uneventful pregnancies and appear neurologically normal at birth and for a few months thereafter (Christie, Bay, Kaufman, Bakay, Borden, & Nyhan, 1982; Dizmang & Cheatham, 1970; Hoefnagel, 1965; Hoefnagel, Andrew, Mireault, & Berndt, 1965; Lesch & Nyhan, 1964; Nyhan, 1973). During the first year, choreoathetoid movements and spastic cerebral palsy develop (Hoefnagel, Andrew, Mireault, & Berndt, 1965; Nyhan, 1973). Babies may be irritable, perhaps because of the painful presence of crystals of uric acid in the urine and contractures may develop (Dizmang & Cheatham, 1970). Because of spastic cerebral palsy, the movements of the children are very awkward. Violent choreoathetoid movements occur, during which the limbs oscillate wildly. Ophistotonic posturing (backward flexing of the trunk and neck) also occurs (Fernald, 1976). These movements can be dangerous to the children and to others, especially since the movements may come to some extent under voluntary control, and may be used to intentionally injure others (Nyhan, 1973).

Many children with Lesch-Nyhan Syndrome can speak, although speech is dysarthric and hard to understand (Libby, Polloway, & Smith, 1983; Nyhan, 1973). Both speech and choreoathetoid movements tend to increase during periods of excitement or irritability (Nyhan, 1973).

Although L-N is associated with mental retardation, it is not invariably so: some individuals have been clearly demonstrated to function at or near normal intelligence (Scherezer & Ilson, 1969). The extreme physical disabilities of individuals with Lesch-Nyhan Syndrome make assessment with norm-referenced tests such as the Wechsler series and the Stanford-Binet difficult (Carter, 1975 Fernald, 1976). Despite often bizarre appearance due to contractures and loss of body parts due to SIB, the children are said to be “unusually engaging” (Nyhan, 1973), and smile and laugh frequently (Fernald, 1976). Nevertheless, they have been noted to be aggressive towards others. Some authors have suggested that this aggressive behavior has the same curious compulsive nature as the self-injurious behavior which will be described below (Libby, Polloway, & Smith, 1983; Nyhan, 1973). However, aggressive behavior does not occur in all individuals with L-N, and it varies in form when it does occur, whereas SIB is usually invariant (Fernald, 1976). Additionally, it is often difficult to determine whether behaviors are truly aggressive, or merely choreoathetoid movements not under voluntary control (Fernald, 1976).

Severe self-injurious behavior occurs in almost all individuals with Lesch-Nyhan Syndrome. The classic pattern is compulsive biting of the fingers, tongue, or lips. Other self-injurious behaviors include head-banging, eye gouging, and picking at wounds, especially near the mouth (Dizmang & Cheatham, 1970).

Self-injurious behavior does not occur in infancy, but typically develops when the child is one or two years of age (Wurtele, King, & Drabman, 1984). The average age of onset of SIB in a sample of 19 individuals was 26 months (Christie, et al. 1982). Diagnosis is often not made until the child is brought to the attention of a physician because of self-mutilation (Christie, et al. 1982). Parents are often able to associate the start of the SIB with a specific injury. To illustrate:

One child began to bite the inside of his mouth and his tongue shortly after a fall from his crib that occurred while he was in the hospital for diagnostic tests. He was one year old at that time. Shortly before he was two years old he began to bite his fingers, and when he was restrained from doing this he began to bite his lips.

—Dizmang and Cheatham, 1970, p. 673

Biting of fingers and mouth parts is so severe that lips may be chewed away and the tongue or fingers amputated(Nyhan, 1973). Clinical descriptions of L-N are sometimes accompanied by photographs which graphically illustrate the tissue loss associated with L-N (cf Hoefnagel, 1965). This loss of tissue distinguishes the SIB of persons with Lesch-Nyhan Syndrome from other mentally retarded individuals with SIB, who may have a great deal of scar tissue, but who rarely show such extreme tissue loss (Fernald, 1976; Nyhan, 1973).

The behavior which accompanies SIB in individuals with Lesch-Nyhan disorder is curious in its own right, and usually warrants a paragraph or two in review articles. There seems to be agreement that the children feel pain, and are very frightened of hurting themselves. They often scream in pain during SIB, and sometimes in anticipation of the actual biting (Fernald, 1976). They may sit on their hands or wedge their arms in their wheelchairs in attempts to self-restrain. Some children refuse to talk about their SIB. One individual with L-N told researchers “I don’t bite myself. It’s my teeth” (Dizmang & Cheatham, 1970, p. 133). Nyhan (1973, p. 43) noted that “When protective coverings or restraints are removed their personality changes… (from smiling and laughing easily)… They appear terrified. They scream and yet compulsively they bite at themselves… As they get older they learn to call for help.”

The following vignette is a poignant example of the powerful impulse and lack of control with which these children struggle. On one occasion the observer and the patient’s physician, with whom the patient had a good relationship, were talking with each other in the presence of the patient. The patient’s doctor carefully but purposefully removed the restraint from one hand as the boy remained deeply engrossed in our conversation. Gradually the patient began to realize his arm was free and his smile slowly changed into a frown; he began to squirm anxiously in his wheelchair, never looking at his hand and making a visible effort not to take his eyes away from us. He slowly tried to get his arm under the arm of the wheelchair as a form of self-restraint. He succeeded in doing this, but by then he was no longer involved in the conversation and was slowly losing the battle with himself as he began to bend his head over and extend his finger toward his mouth. At the last moment his doctor reached down, took a firm hold on his hand, and said, “Michael, you know I won’t let you bite yourself,” at which point the patient quickly relaxed and smiled with great relief.

—Dizmang & Cheatham, 1970, p. 134

Despite the apparently compulsive nature of this SIB, it is thought that individuals with L-N may (at least sometimes) injure themselves because of reinforcing conditions external to themselves (Dizmang & Cheatham, 1970). External events are certainly a factor in self-injurious behavior in other individuals (Ferster, 1961; Skinner, 1953).

 

Mechanical Interventions

The standard treatments for the SIB associated with Lesch-Nyhan Syndrome are mechanical restraints and extraction of teeth. Mechanical restraints are usually applied noncontingently (Letts & Hobson, 1975). The most commonly-used devices seem to be mittens and elbow restraints (Libby, Polloway, & Smith, 1983). Ball, Datta, Pios, & Constantine (1985) were successful in reducing attempts at self-injury and the number of hand-mouth contacts by use of adjustable elbow restraints in two individuals with L-N.

Extraction of teeth is common and has been successful in some cases (Christie et al. 1982; Dizmang & Cheatham, 1970; Watts, et al. 1974), although it should be cautioned that other forms of SIB could arise upon extraction of teeth.

Mechanical restraints and certainly extraction of teeth are not considered to be morally or legally suitable interventions for most self-injurious behavior (Martin, 1975; Picker, Poling, & Parker, 1979). However, the severity of the SIB associated with L-N is such that many children manage to severely damage themselves despite restraints, and mechanical interventions must sometimes be used for their own protection (Libby, Polloway, & Smith, 1983). Additionally, the children seem to want to be restrained, and often become agitated when restraints are removed and remain agitated until the restraints are reapplied (Christie, et al. 1982; Dizmang & Cheatham, 1970; Fernald, 1976; Gilbert, Spellacy & Watts, 1979).

Nevertheless, less restrictive forms of treatment should be used whenever possible.

 

Chemical Interventions

A number of attempts have been made to control L-N by administration of chemicals. The reasoning is this: if SIB is caused by an imbalance of chemicals, and if the chemicals can be brought back into balance, then there should be a reduction in the rate of SIB.

It was at first thought an excess of uric acid caused central nervous system symptoms. An accepted medical treatment for L-N is administration of allopurinol, which brings uric acid production within normal limits. This has been done in some individuals from birth; it relieves the gout symptoms associated with L-N, but cerebral palsy and SIB develop on schedule (Nyhan, 1973). It therefore seems that central nervous symptoms are unrelated to purine metabolism.

SIB in L-N does not seem to be associated with physical damage of the brain. Brains of individuals who had L-N have been found to be morphologically indistinct from other brains (Crussi, Robertson, & Hiscox, 1969; Mizuno, Konishi, & Akaoka, 1976; Sass, Itabashi, & Dexter, 1965). Lloyd, et al. (1981) found biochemical irregularities in Lesch-Nyhan brains that extended beyond the purine system. They suggested that there is a general deficit of some neurotransmitters and enzymes (dopamine, homovanillic acid, dopa decarboxylase, tyrosine hydroxylase, and catechol-o-methyltransferase) and a surplus of others (monoamine oxidase and dihydroxyphenylacetic acid).

There does seem to be an association between SIB and brain chemicals. Severe SIB in animals has been elicited by administration of sympathomimetic compounds (Boyd, Dolman, Knight, & Sheppard, 1965; Genovese, Napoli, & Bolega-Zonta, 1969), and aggressive behavior has been shown to be related to brain levels of serotonin (DiChiara, Camba, & Spano, 1971).

Evidence that altering levels or serotonin and dopamine affects SIB in Lesch-Nyhan Syndrome is equivocal. In a brief note in The Lancet, Mizuno & Yugari (1974) reported elimination of SIB in four patients with L-N by administration of L-5-hydroxytryptophan (5-HTP). They chose this drug (which alters brain levels of serotonin) because they considered SIB to be self-aggression, and 5-HTP had been reported to reduce aggressive behavior in rats (Kulkarni, Rahwan, & Bocknik, 1973). SIB reportedly stopped after 1-3 days. When 5-HTP was discontinued, SIB returned to baseline levels.

Castells, Chakrabarti, Winsberg, Hurwic, Perel, & Nyhan (1979) administered 5-HTP to an L-N infant who had not yet developed SIB. On two occasions when the drug was discontinued, they found that SIB appeared; they speculated that 5-HTP had kept SIB from occurring.

Nyhan, Johnson, Kaufman, & Jones (1980) found short-term effects of 5-HTP and Carbidopa on nine individuals with L-N, and a significant reduction of SIB. However, the effect faded within 1-3 months and could not be reproduced a year later. This study utilized independent observers, who watched videotapes and made judgements about SIB.

Anderson, Herrmann, & Dancis (1976) administered 5-HTP to four patients with L-N, but observed no reduction of SIB, either at home or in the hospital. This study was methodologically more sound than either Kulkarni, Rahwan, & Bocknik (1973), or Anderson, Herrmann, & Dancis (1976), as it was done with placebo in a double-blind fashion.

In a double-blind study with a single subject with L-N, Frith, Johnstone, Joseph, Powell, & Watts (1976) found that choreoathetoid movements occurred less frequently after administration of 5-HTP. They also found a general sedative effect, but found no difference in SIB.

Ciaranello, Anders, Barchas, Berger, & Cann, (1976) did not find an effect of 5-HTP on SIB in a study with an individual with L-N.

There is then, little evidence 5-HTP can lastingly reduce SIB in individuals with Lesch-Nyhan Syndrome.

Goldstein, Anderson, Reuben, & Dancis (1985), in a double-blind study with placebo, found fluphenazine (Prolixin) reduced SIB in an individual with L-N, and suggested that SIB in L-N is caused by domamine supersensitivity. Replication has not been reported.

Two other unreplicated studies are of interest. Richardson & Zaleski (1983) reported reduction of SIB in an adolescent with L-N after administration of naloxone, an opiate antagonist. Since endorphin/enkephal in the system seem to be involved in pain reduction (Bunney, Pert, Klee, Costa, Pert, & Davis, 1979), this finding suggests that pain may be a reinforcing stimulus in L-N.

In a case study, Ghadimi, Bhalla, & Kirchenbaum reported the effect of a high-protein diet with purine precursors upon a child with L-N. They noted that by analogy with treatment for gout, individuals with L-N were often fed a low purine, low protein diet. Although there were methodological difficulties (for example, there was no objective rating scale), considerable improvement was reported in the physical condition (which is apparent in the before-and-after photographs) and the report of reduction of self-injurious behavior begs replication.

In summary, although there are several promising findings which remain unreplicated, to date, a chemical intervention which demonstrably and reliably reduces SIB in Lesch-Nyhan Syndrome has not been established.

 

Behavioral Interventions

If SIB in Lesch-Nyhan Syndrome is affected by environmental contingencies, then manipulation of reinforcement contingencies should prove effective in eliminating the behavior. If, however, SIB in L-N is a function of brain chemicals, or is otherwise organically caused, it might prove resistant to behavioral intervention. Behavioral approaches are effective in reducing SIB in Lesch-Nyhan Syndrome, but there seem to be differences between individuals with L-N and other individuals. For instance, the application of aversive stimuli, which reduces responding in most persons (Lovaas & Simmons, 1969; Picker, Poling, & Parker, 1979), does not seem to reduce SIB in L-N, but instead accelerates it (Anderson, Dancis, & Alpert, 1978; Nyhan, 1976). This is an interesting phenomenon, and one certainly worthy of further study. For instance, it would be interesting to determine whether punishment (the application of aversive stimulation) and negative punishment (removal of a stimulus contingent upon a behavior) are equally ineffective in reducing SIB in L-N. It would be equally interesting to see whether procedures such as time-out from positive reinforcement (Wolf, Risley, Johnson, Harris, & Allen, 1967) and overcorrection (Foxx & Azrin, 1973) would reduce SIB in individuals with L-N.

Extinction can be effective in reducing undesirable behaviors. Because there is often an initial increase in the frequency of the behavior, and because, depending upon the reinforcement history of the individual, extinction may occur only after exhibition of thousands of responses, there may be ethical problems in using this procedure to reduce the freuqency of SIB (Nyhan, 1976; Wurtele, King, & Drabman, 1984). For example, Lovaas & Simmons (1969) found that a 7-year-old boy exhibited more than 10,000 instances of SIB before extinction occurred. Considering the severity of SIB in the Lesch-Nyhan Syndrome, it might be expected that extinction would be only rarely used. However, a number of ­workers have used extinction procedures. Duker (1975) used extinction with a nine-year-old L-N boy and found that biting decreased, but head-banging became a serious problem. It should be noted that prior observation of the boy led Duker to speculate SIB was under environmental control.

Bull & LaVecchio (1978) also used an extinction procedure, with some success. Gilbert, Spellacy, & Watts (1979) also using extinction and differential reinforcement of other behavior (DRO), found a decrease of SIB in a boy with L-N. In this study, the child was not allowed to bite himself; instead, the hand was intercepted and returned to his lap. In all cases, extinction did not generalize to other settings (Wurtele, King, & Drabman, 1984). Wurtele, King, & Drabman (1984) systematically observed a 13-year-old with L-N, and found that SIB increased when he was not getting attention from adults. The typical outcome of SIB was attention from a nurse. These researchers employed a DRI (differential reinforcement of incompatible behavior) procedure. The child was fitted with a plastic mouthpiece which made biting impossible, and then trained to employ the mouthpiece. Wearing the mouthpiece was a sign to staff to pay attention to the child. There was an initial increase in biting, but the rate of biting had decreased to zero by the third day. During times when the child was expected to have his mouth unemcumbered (mealtimes), a pair of gloves was substituted for the mouthpiece. A fading procedure was then begun. In this case, there did seem to be generalization to other settings. Buzas, Ayllon, & Collins (1981) used a DRI procedure to reduce SIB in an individual with L-N. They also found generalization across settings. A follow-up seven months after intervention showed that the treatment effect was maintained.

Although individuals with L-N do not decrease their SIB when punished, other behavioral techniques seem to be effective in reducing SIB in the Lesch-Nyhan Syndrome. To date, DRI has been the most effective method and least intrusive method of producing a lasting decrease in SIB that generalizes across settings.

 

Conclusion

Of the various methods which have been used in attempts to control the self-injurious behavior associated with Lesch-Nyhan Syndrome, behavioral interventions, especially DRI and DRO, have been the most effective, are the least intrusive, and show the most promise. Because punishment has been shown to increase, rather than descrease SIB in L-N, punishment procedures should be avoided. Mechanical interventions, while adequate for dealing with the immediacy of saving a child from serious self-injury, are in the long run intrusive and unethical, and should therefore be avoided. Chemical interventions are problematic due to inadequate knowledge of brain chemistry, and should be avoided.

In reviewing the literature, it has become clear to me that there are similarities between SIB in L-N and movement disorders such as Gilles de la Tourette Syndrome (Fernald, 1976), Parkinson’s disease (Lloyd, et al. 1981), and tardive dyskinesia. It is equally clear a good deal of SIB in L-N patients is environmentally controlled. Although various treatments in the literature suggest it, there has never been a clear attempt to determine whether there are two distinct types of SIB in the Lesch-Nyhan Syndrome: a compulsive behavior which is not under environmental control, and a learned response which is effectively used for producing desired environmental events. It would be of interest to have an ethogram of SIB in this syndrome; that is, a clear, qualitative description of the various topographies of the behavior. It would be of especial interest to see whether these two types of SIB (if they are indeed distinct) respond differentially to chemical and behavioral interventions.

 

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