Deep brain stimulation (DBS)
In DBS, high-frequency electrical stimulation is applied via an electrode to specific brain areas, where it inhibits neuronal activity in overactive regions. To date, several Lesch-Nyhan disease (LND) patients who have received DBS, targeted at the globus pallidus pars interna, have been reported in the literature.[55]Taira T, Kobayashi T, Hori T. Disappearance of self-mutilating behavior in a patient with Lesch-Nyhan syndrome after bilateral chronic stimulation of the globus pallidus internus. Case report. J Neurosurg. 2003 Feb;98(2):414-6.
http://www.ncbi.nlm.nih.gov/pubmed/12593632?tool=bestpractice.com
[56]Pralong E, Pollo C, Coubes P, et al. Electrophysiological characteristics of limbic and motor globus pallidus internus (GPI) neurons in two cases of Lesch-Nyhan syndrome. Neurophysiol Clin. 2005 Nov-Dec;35(5-6):168-73.
http://www.ncbi.nlm.nih.gov/pubmed/16530134?tool=bestpractice.com
[57]Cif L, Biolsi B, Gavarini S, et al. Antero-ventral internal pallidum stimulation improves behavioral disorders in Lesch-Nyhan disease. Mov Disord. 2007 Oct 31;22(14):2126-9.
http://www.ncbi.nlm.nih.gov/pubmed/17853483?tool=bestpractice.com
[58]Piedimonte F, Andreani JC, Piedimonte L, et al. Remarkable clinical improvement with bilateral globus pallidus internus deep brain stimulation in a case of Lesch-Nyhan disease: five-year follow-up. Neuromodulation. 2015 Feb;18(2):118-22.
http://www.ncbi.nlm.nih.gov/pubmed/25603976?tool=bestpractice.com
[59]Deon LL, Kalichman MA, Booth CL, et al. Pallidal deep-brain stimulation associated with complete remission of self-injurious behaviors in a patient with Lesch-Nyhan syndrome: a case report. J Child Neurol. 2012 Jan;27(1):117-20.
http://www.ncbi.nlm.nih.gov/pubmed/21940691?tool=bestpractice.com
[60]Air EL, Ostrem JL, Sanger TD, et al. Deep brain stimulation in children: experience and technical pearls. J Neurosurg Pediatr. 2011 Dec;8(6):566-74.
http://www.ncbi.nlm.nih.gov/pubmed/22132914?tool=bestpractice.com
[61]Tambirajoo K, Furlanetti L, Hasegawa H, et al. Deep Brain Stimulation of the Internal Pallidum in Lesch-Nyhan Syndrome: Clinical Outcomes and Connectivity Analysis. Neuromodulation. 2021 Feb;24(2):380-91.
http://www.ncbi.nlm.nih.gov/pubmed/32573906?tool=bestpractice.com
[62]Abel TJ, Dalm BD, Grossbach AJ, et al. Lateralized effect of pallidal stimulation on self-mutilation in Lesch-Nyhan disease. J Neurosurg Pediatr. 2014 Dec;14(6):594-7.
http://www.ncbi.nlm.nih.gov/pubmed/25303157?tool=bestpractice.com
Some showed remarkable improvements in motor dysfunction, and even self-injury, but these may not be sustained, and complications have frequently been noted.[63]Visser JE, Cotton AC, Schretlen DJ, et al. Deep brain stimulation in Lesch-Nyhan disease: outcomes from the patient's perspective. Dev Med Child Neurol. 2021 Aug;63(8):963-68.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350791
http://www.ncbi.nlm.nih.gov/pubmed/33689173?tool=bestpractice.com
More studies are needed before DBS can be considered effective and safe in LND.
Selective dopamine receptor antagonists
A trial of the selective dopamine D1/D5 receptor antagonist ecopipam in LND patients was terminated early due to unanticipated side effects.[64]Khasnavis T, Torres RJ, Sommerfeld B, et al. A double-blind, placebo-controlled, crossover trial of the selective dopamine D1 receptor antagonist ecopipam in patients with Lesch-Nyhan disease. Mol Genet Metab. 2016 Jul;118(3):160-6.
http://www.ncbi.nlm.nih.gov/pubmed/27179999?tool=bestpractice.com
However, because the drug appeared to reduce self-injury in most of the limited number of patients enrolled, ecopipam could be a useful treatment for self-injurious behavior in LND. Further studies are warranted before it can be considered effective and safe in LND.