Tratamiento de la sialorrea en niños con patología neurológica / Drooling therapy in children with neurological disorders

Introducción. La sialorrea es la incapacidad para retener la saliva dentro de la boca y su progresión al tracto digestivo, y es un problema frecuente en pacientes pediátricos con patología neurológica, por lo que se están utilizando diferentes medidas para su tratamiento. Objetivo. Evaluar la eficacia y seguridad del trihexifenidilo, la escopolamina y la infiltración de toxina botulínica en el tratamiento del babeo en niños con patología neurológica. Pacientes y métodos. Es un estudio de tipo abierto y prospectivo. Incluye pacientes atendidos en el servicio de neurología que presentaban babeo excesivo, con repercusión en su calidad de vida, entre 2009 y 2013. Resultados. En 46 pacientes se indicó tratamiento con trihexifenidilo oral, y se obtuvo buena respuesta en 15 (32,6%), tres con efecto transitorio y el resto mantenido. Presentaron efectos secundarios tres pacientes (6,5%). De los 11 pacientes a los que se indicaron parches de escopolamina, se halló efecto beneficioso en cuatro (36,36%), uno fue retirado por falta de eficacia y seis por efectos secundarios. Veinticinco pacientes fueron infiltrados con toxina botulínica, con disminución significativa del babeo en 16 (64%) tras la primera infiltración. No observamos cambios significativos en nueve casos. Sólo uno presentó efectos secundarios (disfagia leve). Conclusiones. Por no haber una opción terapéutica totalmente eficaz para los pacientes con sialorrea, recomendamos iniciar el tratamiento con trihexifenidilo; como segunda opción, los parches de escopolamina, y como tercera opción, la toxina botulínica. La infiltración de toxina botulínica en glándulas salivales se muestra como una alternativa eficaz y segura según nuestra serie (AU)

Introduction. Drooling is the inability to retain saliva in the mouth and its progression to the digestive tract, being a common problem in pediatric patients with neurological disorders. Three different treatment options are available. Aim. To assess the effectiveness and safety of trihexyphenidyl, scopolamine and botulinum toxin infiltration in the treatment of drooling in children with neurological disorders. Patients and methods. This is an open and prospective type study. We include patients treated in the Neurology Service that present excessive drooling, affecting their quality of life, between 2009 and 2013. Results. We enrolled 46 patients in the study. The treatment with oral trihexyphenidyl was indicated in 46, obtaining good result in 15 (32.6%), three with temporary effect and the rest with lasting effect. Three patients presented side effects (6.5%). Four out of 11 (36.36%) patients treated with scopolamine patch had beneficial effects. One was withdrawn due to lack of efficacy and six due to side effects. Twenty-five patients were infiltrated with botulinum toxin, with a significant decrease of drooling in 16 patients (64%) after the first injection. We observed no significant changes in nine patients. Only one out of 25 showed side effects (mild dysphagia). Conclusions. Currently there is not a fully effective therapeutic option for drooling. We recommend starting treatment with trihexyphenidyl. A second option could be the scopolamine patch and botulinum toxin as a third option. Botulinum toxin infiltration in salivary glands is shown as an effective and safe alternative in our study (AU)

Genetic association between the DRD4 promoter polymorphism and clozapine-induced sialorrhea.

The use of clozapine, an effective antipsychotic drug used in treatment-resistant schizophrenia, is associated with adverse effects. Sialorrhea is one such effect, which can be distressing for many patients. Studies on the pharmacogenetics of the adverse effects of clozapine are limited. The aim of the present study was to determine whether clozapine-induced sialorrhea is associated with a 120 base-pairs (bp) tandem duplication polymorphism in the dopamine receptor subtype D4 (DRD4) gene. Ninety-five patients, mean age 35.43±9.43 years, with treatment-resistant schizophrenia and on clozapine were included in the study. Development of sialorrhea in response to the drug, as manifested by drooling of saliva, was documented in 45 (47.4%) patients. Genotyping of the patients was carried out to detect the presence of the polymorphism of interest. Clozapine-induced sialorrhea was found to be associated significantly with the 120-bp duplication in DRD4. The association was found to fit a log-additive model with an odds ratio of 2.95 (95% confidence interval 1.51-5.75; P=0.0006). Thus, the presence of the 120-bp duplication in DRD4 appears to confer a risk for sialorrhea in response to clozapine therapy. The underlying pathophysiology and clinical significance of this phenomenon warrant further investigation.

Polymorphism in alpha 2A adrenergic receptor gene is associated with sialorrhea in schizophrenia patients on clozapine treatment.

OBJECTIVE: Clozapine-induced sialorrhea (CIS) is a common, inconvenient and socially stigmatizing adverse effect. The pathophysiology of CIS may be related to the effect of clozapine on the muscarinic and adrenergic receptors as well as the disruption of the circadian rhythms. The aim of this study was to find out if polymorphisms in muscarinic M1 and M3 receptor genes (CHRM1 and CHRM3), adrenoceptor alpha 2A gene (ADRA2A) or clock circadian regulator gene (CLOCK) are associated with CIS. METHODS: Two hundred and thirty-seven clozapine-treated Finnish schizophrenia patients were genotyped for CHRM1, CHRM3, CLOCK and ADRA2A polymorphisms, and their salivary dysfunction was assessed with two questions. Twenty-six of these patients had previously been on medication to treat CIS. Comparisons of the genotypes between patients with excessive versus non-excessive salivation were analysed. Genotype distributions between patients and control group and haplotypes were also studied. RESULTS: CHRM1, CHRM3 and CLOCK polymorphisms and haplotypes were not associated with CIS. ADRA2A (rs1800544) genotype was associated with CIS (p = 0.029). In patients with CIS, CC genotype (n = 103) was more common than in G-allele carriers (n = 79) (p = 0.013, OR 2.13, 95% CI: 1.17-3.88). No differences were found in the distributions of genotypes between patients and controls. CONCLUSIONS: ADRA2A genotype was associated with CIS.

MRI in a patient with the Worster-Drought syndrome.

We describe a patient with the Worster-Drought syndrome (congenital suprabulbar paresis), thought to be a failure of development of the corticobulbar tracts. MRI showed bilateral perisylvian cortical dysplasia.

Increased major salivary gland secretion in familial dysautonomia.

Familial dysautonomia (FD), an autosomal recessive peripheral nervous system disorder, affects almost exclusively children of Jewish Ashkenazi origin and causes profound generalized autonomic dysfunction. Excessive drooling is frequent and is traditionally attributed to swallowing difficulties. Although true hypersalivation has been postulated, no quantitative assessment of the salivary secretion rate has yet been reported. The authors determined this rate in 13 children with FD and 28 healthy controls. Resting parotid, submandibular/sublingual and unstimulated whole salivary secretion rates were significantly elevated in children with FD. The known relation of salivary function with age was found in controls only. This apparently major contribution of salivary hyperfunction to excessive drooling in FD may be attributable to salivary gland denervation supersensitivity, as this mechanism is present in the cardiovascular system and the pupil in FD.