[Tear your eyes out ! A case of bilateral auto-enucleation]. / «Arrache-toi les yeux !¼ À propos d'un cas d'auto-énucléation bilatérale.

Bilateral autoenucleation is an extremely rare form of ocular self-mutilation. This gesture usually occurs in psychotic patients. In a moment of madness, a 28-year-old man brutally tore out both of his eyes. He was in acute relapse of schizophrenia after having interrupted all neuroleptic treatment for 6 months. Four days after admission, surgical enucleation was the only possible outcome. Facing the complexity of this clinical case, the ophthalmologist has a central role in the organization of long-term surgical, neurological and psychiatric care.

L'auto-énucléation bilatérale est une forme d'automutilation oculaire rarissime. Ce geste est observé presque toujours chez des patients psychotiques. Dans un moment de folie, un homme de 28 ans, s'est brutalement arraché les deux yeux. Il se trouvait en rechute aiguë de schizophrénie après avoir interrompu tout traitement neuroleptique depuis 6 mois. Quatre jours après son admission, l'énucléation chirurgicale fut la seule issue possible. Face à la complexité de ce cas clinique, l'ophtalmologue aura un rôle central dans l'organisation des soins chirurgicaux, neurologiques et psychiatriques au long cours.

[Treatment of borderline personality disorder with opioid antagonists: buprenorphine, nalmefene, naloxone and naltrexone in the treatment of dissociative symptoms, self-mutilation and suicidal behavior]. / Tratamiento del Trastorno límite de la personalidad con antagonistas opioides: buprenorfina, nalmefeno, naloxona y naltrexona en el tratamiento de síntomas disociativos, automutilaciones y conducta suicida.

OBJECTIVE: Recent theory has proposed that a dysfunction of the opioid system modulates mood, reward and pain; seems to be unstable in people with Borderline Personality Disorder. Our purpose is to analyze the evidence on the efficacy of the use of buprenorphine, nalmefene, naloxone and naltrexone, in the treatment of dissociative symptoms, self-mutilation and suicidal behavior of these patients. METHOD: We conducted a systematic search of MEDLINE and LILACS databases, to retrieve relevant articles. Included studies were experimental and observational designs of borderline personality samples in which dissociative symptoms, self mutilation or suicidal behavior was reported as an outcome and evaluated with some impact measures. RESULTS: A total of eight studies were reviewed. These provided interesting expectations about posible treatment lines in Borderline Personality Disorder using opioid antagonists. The subgroup most benefited was the one who has analgesia and highest number of diagnostic criteria. CONCLUSIONS: Studies of higher methodological quality are needed, in larger population samples and using control of confounding variables that allow us to estimate a value power calculation, and thus be able to support firm conclusions.

An open-label pilot study of N-acetylcysteine for skin-picking in Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder caused by an abnormality on the long arm of chromosome 15 (q11-q13) that results in a host of behavioral characteristics including excessive interest in food, skin picking, difficulty with a change in routine, and obsessive and compulsive behaviors. Skin-picking can result in serious and potentially life-threatening infections. Recent evidence suggests that the excitatory neurotransmitter glutamate is dysregulated in obsessive-compulsive behaviors, and modulation of the glutaminergic pathway may decrease compulsive behaviors, such as recurrent hair pulling or skin-picking behaviors. N-acetylcysteine (NAC), a derivative of the amino acid cysteine, is thought to act either via modulation of NMDA glutamate receptors or by increasing glutathione in pilot studies. Thirty-five individuals with confirmed PWS (ages 5-39 years, 23 females/12 males) and skin-picking behavior for more than 1 year were treated with N-acetylcysteine (Pharma-NAC®) at a dose of 450-1,200 mg/day. Skin-picking symptoms and open lesions were assessed after 12 weeks of treatment by counting and measuring lesions before and after the medication. All 35 individuals had improvement in skin-picking behaviors. Ten (29%) individuals (six males and four females) did not have complete resolution of skin-picking behavior, but had significant reduction in the number of active lesions. Longer-term, placebo-controlled trials are needed to further assess the potential benefit of this treatment.

Safety and Efficacy of Botulinum Toxin in the Treatment of Self-Biting Behavior in Lesch-Nyhan Disease.

BACKGROUND: Lesch-Nyhan disease (LND) is a disease of purine metabolism linked to chromosome X due to the absence or near-absence of enzyme hypoxanthine-guanine phosphoribosyltransferase. Patients with LND have a compulsive autoaggressive behavior that consists of self-mutilation by biting. METHODS: The objective of this study was to explore the safety and efficacy of botulinum toxin (BoNT) injected into the masticatory muscles and biceps brachii to reduce self-mutilation in patients with LND. We retrospectively analyzed six patients with LND who were treated with BoNT to prevent automutilatory behavior. RESULTS: The patient ages when started on treatment with BoNT were 4, 4.5, 6.6, 7.9, 13.9, and 32.3 years. Patients received a mean number of injections of 20, ranging from 3 to 29, over a period that ranged from 1.5 to 7.1 years. The maximum total dose of Botox was 21.3 units/kg mean and the maximum total dose of Dysport was 37.5 units/kg mean. A total of 119 injections were performed. Of these 113 (95%) were partially or completely effective. Only three of 119 injections (2.5%) produced adverse effects. CONCLUSIONS: Botulinum toxin is useful and safe for the treatment of self-biting behavior in patients with LND.

Antipsychotics in the treatment of autism.

Atypical antipsychotics have become indispensable in the treatment of a variety of symptoms in autism. They are frequently used to treat irritability and associated behaviors including aggression and self injury. They may also be efficacious for hyperactivity and stereotyped behavior. This review presents the rationale for the use of this drug class in autism and reviews the most important studies published on this topic to date. Significant adverse effects, including weight gain and the possibility of tardive dyskinesia, are reviewed. Future research directions are discussed.

Reduction of self-mutilating behavior and improved oromotor function in a patient with Lesch-Nyhan syndrome following botulinum toxin injection: A case report.

Lesch-Nyhan syndrome is a genetic metabolic disorder often involving dystonia and self-mutilating behavior. This case report describes a 13-year-old boy with Lesch-Nyhan syndrome and self-mutilating behavior who received botulinum toxin injections to his bilateral masseter muscles after failing multiple other treatments. Following injections, the patient had reduction in self-biting, along with improvements in speech, mastication and feeding observed in speech therapy. Botulinum toxin injections to the masseters may help to improve oromotor function and reduce self-mutilating behaviors in children with Lesch-Nyhan syndrome who have failed more conservative treatments, providing opportunity for improved functional status and patient safety. Further investigation is indicated to establish optimal dosing. Additionally, the mechanism for the reduction of self-mutilating behavior is unclear and justifies additional investigation.

Naloxone and self-mutilation.

A 15-year-old male with a long history of self-mutilation resembling the Lesch-Nyhan syndrome, but with normal uric acid levels, was treated with naloxone. Pain-inducing behavior decreased in the evenings following infusion of the drug, and was markedly reduced for 2 days following the treatment period. Though not recommended as therapy, the observations suggest that naloxone may play a role in the regulation of endorphin/enkephalin neural systems.

Naltrexone attenuates self-injurious behavior in mentally retarded subjects.

The effect of naltrexone on the frequency of self-injurious behavior (SIB) was investigated in 6 male subjects with profound mental retardation. Following a double-blind placebo-controlled crossover design, naltrexone was administered in a dose of 50 mg once daily for 3 consecutive weeks. In 2 of 5 subjects, a significant decrease of SIB frequency could be demonstrated, and in 1, a tendency to a reduction was found. No effect on duration of restrain time was found in 3 subjects. These data suggest that disturbances of the endogenous opioid systems may be involved in the pathophysiology of SIB of certain patients.

Positive effects of carbamazepine on behavioral dyscontrol in borderline personality disorder.

In a double-blind crossover trial, carbamazepine, an anticonvulsant with primary effects on subcortical limbic structures, decreased the severity of behavioral dyscontrol in 11 women with borderline personality disorder significantly more than placebo. The authors emphasize the preliminary nature of their findings and discuss alternative hypotheses regarding mechanisms by which carbamazepine might influence behavioral dyscontrol.

Continuous naloxone administration via osmotic minipump decreases autotomy but has no effect on nociceptive threshold in the rat.

Rats with unilaterally sectioned sciatic nerves were continuously administered naloxone HCl (80 or 800 micrograms/h) or equivalent volumes of saline (1 or 10 microliters/h) subcutaneously via osmotic minipumps over a 2 or 5 week period. Rats receiving 80 micrograms/h naloxone for 5 weeks exhibited significantly less self-mutilation (autotomy) of the denervated foot than saline controls or rats receiving 80 micrograms/h naloxone for 2 weeks. The nociceptive threshold of intact rats infused with the same dose of naloxone was tested on a hot plate. In these animals there was no influence on the nociceptive threshold during naloxone administration for 1 week. Autotomy was also reduced in rats infused with 800 micrograms/h naloxone. The nociceptive threshold of intact rats infused with this dose of naloxone or an equivalent volume of saline (10 microliters/h) was increased, suggesting that the presence of the larger osmotic pump caused analgesia.

The effect of intrathecal endomorphin-2 on the flexor reflex in normal, inflamed and axotomized rats: reduced effect in rats with autotomy.

Endomorphin-2, a newly discovered endogenous opioid peptide and agonist at the mu-opioid receptor, was injected intrathecally in normal rats and animals with unilateral peripheral inflammation or sciatic nerve section and its effect on the nociceptive flexor reflex was analysed. In normal rats, intrathecal endomorphin-2 induced a strong and dose-dependent depression of the reflex, which was naloxone-reversible. The effect of intrathecal endomorphin-2 was fairly brief, lasting for about 20-30 min at the highest dose, 4 microg. The effect of endomorphin-2 in inflamed rats was not significantly different from that in normals. After nerve section some rats developed autotomy behavior. In these rats endomorphin-2 had significantly reduced effect. However, the reflex depressive effect of intrathecal endomorphin-2 was unchanged in axotomized rats without autotomy. It is suggested that intrathecal endomorphin-2 has antinociceptive effect in the rat spinal cord under normal and inflammatory conditions. After peripheral nerve injury the sensitivity to endmorphin-2 may be reduced in rats that exhibit ongoing neuropathic pain-like behaviors.

Buspirone therapy for maladaptive behavior and anxiety in developmentally disabled persons.

The authors used buspirone, a new anxiolytic agent that has a low side effect profile, to treat 14 developmentally disabled individuals who demonstrated anxiety as well as aggressive and self-injurious behaviors. Nine of the 14 individuals responded favorably to the drug. The authors present case reports for 3 of the responders and discuss the clinical implications of buspirone therapy.

Dietary supplementation with the inhibitory amino acid taurine suppresses autotomy in HA rats.

Taurine is an inhibitory amino acid in the CNS. When supplied to rats it produces analgesia in some acute pain tests. Here we examined the effect of taurine supplementation on sensitivity to pain in intact rats, and whether perioperative dietary supplementation with taurine in rats would suppress autotomy, a behavior produced by peripheral neurectomy and related to neuropathic pain. Thermal pain sensitivity of intact rats consuming 1% taurine in the drinking solution for 2 weeks was not significantly different from that of control rats. Autotomy levels, determined in rats consuming taurine pre-, post- or perioperatively were significantly lower than in matching control groups. We conclude that taurine plays an important role in the autotomy model, presumably by protecting inhibitory neurons in the CNS against an excitotoxic damage triggered by injury discharge and ectopic input from the severed nerves.

Pharmacologic treatment of severe skin-picking behaviors in Prader-Willi syndrome. Two case reports.

BACKGROUND: Prader-Willi syndrome (PWS) is characterized by hypotonia at birth, hypogonadism, early childhood obesity, and mental deficiency. Other behavioral symptoms that become prominent during adolescence and adulthood include temper outbursts, stealing and hoarding food, and skin picking. The self-excoriating skin picking behavior observed in individuals with PWS is quite common and can lead to persistent sores and infections, even requiring hospitalization. OBSERVATION: Two patients with PWS who displayed repetitive, self-mutilatory behavior of skin picking are described. They were both treated successfully with different doses of fluoxetine, a selective serotonin reuptake inhibitor. CONCLUSIONS: The skin-picking behavior in patients with PWS may be a variant of the spectrum of obsessive-compulsive disorders. Obsessive-compulsive disorders have been successfully treated with serotonin reuptake inhibitors such as fluoxetine. Thus, fluoxetine may be considered an option in the management of skin-picking behavior in patients with PWS.

Suppression of autotomy by N-methyl-D-aspartate receptor antagonist (MK-801) in the rat.

The effects of different doses and time of administration of the N-methyl-D-aspartate (NMDA) receptor antagonist (MK-801) on the development of the autotomy (self-mutilation) were studied in the rats receiving dorsal root ganglionectomy (DRGn). The rats without any treatment and those treated with normal saline immediately after DRGn were the control groups. Three groups of rats were treated with 0.1, 0.5 or 1.0 mg/kg of MK-801 immediately after DRGn, and another three were treated with 1.0 mg/kg of MK-801 2, 4, or 7 days after DRGn. The behavioral observations of these rats were quantified using an autotomy grading scale ranging from 0 to 19, and the scores were compared among these groups. The rats in the control groups manifested autotomy from 5 to 17 days after DRGn and all of them (100%) attained the highest autotomy score. Lower doses (0.1 or 0.5 mg/kg) of MK-801 had no effect on the development of the autotomy. In contrast, higher dose (1.0 mg/kg) of MK-801 administered immediately after DRGn significantly suppressed the autotomy as compared to the control groups (P < 0.01) and only 17% of the rats in this group attained the highest score. The antagonistic effect was retained when the treatment of MK-801 was delayed to 2 days after DRGn, however, it disappeared when the treatment was delayed to 4 or 7 days after DRGn. Thus, the antagonistic effect of MK-801 on the autotomy induced by DRGn was dose-related and time-dependent. The main role of the NMDA receptor in the development of the autotomy was within several days after DRGn.

Chronic amitriptyline decreases autotomy following dorsal rhizotomy in rats.

In the rat, unilateral dorsal cervicothoracic rhizotomy (C5-T1), a proposed model of chronic pain, resulted in autotomy of the ipsilateral limb. The self-mutilation lesions were evaluated daily by means of an autotomy score from the 1st to the 80th postoperatory day. The onset of lesions was variable and attained the maximum degree 8-9 weeks after the dorsal roots section. Chronic administration of amitriptyline (5 and 10 mg/kg/day, i.p., over 30 days), started on the 10th day after rhizotomy, decreased autotomy behavior, an effect which persisted 20 days after treatment withdrawal, and lengthened almost two-fold the lag time between rhizotomy and appearance of lesions. A more pronounced effect was observed with the lowest dose of amitriptyline suggesting the existence of a therapeutic window. Possible mechanisms for the antinociceptive effect of amitriptyline in this model are discussed.

Spinal neurons involved in the generation of at-level pain following spinal injury in the rat.

Using a conjugate of substance P and the ribosome-inactivating protein saporin, neurons expressing the neurokinin-1 receptor in lamina I of the spinal cord were targeted to determine their role in the expression of a spontaneous pain behavior following intraspinal injections of quisqualic acid in the rat. Treatment was carried out at the time of injury in order to prevent the onset of the behavior, and following onset in order to evaluate the potential clinical utility of this intervention. Treatment at the time of injury resulted in significant decreases in onset-time and severity of pain behavior, while treatment at the time of onset led to a significant reduction of the spontaneous self-directed behavior. The results suggest that the substrate for at-level pain following spinal cord injury includes a population of spinal neurons expressing the neurokinin-1 receptor in the superficial laminae of the spinal cord.

Risperidone antagonism of self-mutilation in a Lesch-Nyhan patient.

1. The case is described of a 28-year old male with a diagnosis of Lesch-Nyhan syndrome. 2. Chronic treatment with the atypical neuroleptic risperidone at 4 mg daily has maintained a significant reduction in occurrence of self-mutilation.

Pharmacologic management of aggressivity and self-mutilation in the mentally retarded.

The use of pharmacologic agents in the control of aggression and self-mutilation in the mentally retarded is controversial but at times necessary for the implementation of behavioral treatments. The choice of drug is often empirical, as the specific etiology of aggression is generally unknown. On the other hand, certain rare conditions may be treated specifically. Controlled therapeutic studies are still lacking, as most treatments are symptomatic and nonspecific.