Deep Brain Stimulation (DBS) in the treatment of primary dystonia of the pediatric population: a review

Background: Deep Brain Stimulation (DBS) is a neurosurgical technique widely used for the treatment of several pathologies, such as Parkinson’s Disease and dystonias. Dystonias, primary or secondary, have several determining factors, among which we can mention genetic mutations, that, generally, do not respond satisfactorily to drug treatments. The difficult control of dystonias makes its management complex, since they are progressive, and, as a consequence, surgical options are often necessary. Objectives: To identify the impact of the use of DBS on the prognosis of children with primary dystonia. Methods: The present work consists of an integrative literature review, in which a careful search was carried out from databases available on the internet, such as Google Scholar, MedScape, Scielo and PubMed, using the following keywords combined in pairs: deep brain stimulation, pediatrics and primary dystonia. The research was carried out in English and Portuguese and, at the end, 10 articles published between the years 2017 and 2021 were selected. Results: Through analysis, it was observed that DBS proved to be an excellent therapy, with good results, especially for patients with primary dystonia, who were more susceptible to showing improvements in motor symptoms. Of these patients, those who have a mutation in the DYT1 gene seemed to respond better when it comes to disabling symptoms, as well as those who have known genetic etiologies. Conclusions: Although there is a limited number of studies related to the pediatric population, the use of DBS for dystonias, especially primary ones, seems to be an excellent therapeutic option for patients refractory to drug therapy. In any case, studies aimed at this group are still necessary in order to enrich and support the current evidence.

Genetic evaluation for TOR1-A (DYT1) in Brazilian patients with dystonia

Several genes have been mapped in families or in sporadic cases of dystonia. TOR1-A (DYT1) gene was linked to isolated dystonia. Objective To associate clinical information of patients with dystonia with the TOR1-A gene mutations. Method Eighty-eight patients with dystonia in cervical area (focal, segmental, multifocal and generalized) were recruited at Movement Disorders Clinic of Hospital de Clínicas of the Federal University of Paraná between June of 2008 and June of 2009. They were submitted to the clinical evaluation. DNA was extract from blood and submitted at analysis to TOR1-A mutations by PCR according standard protocols. Results Two patients had c.907GAGdel mutation on TOR1-A gene. These patients, with familial history of dystonia, started his symptoms by legs and had secondary generalization. Conclusion We can suggest that analysis for TOR1-A mutations should be performed only in patients with early onset, generalized and familial dystonia.

TorsinA and DYT1 dystonia: a synaptopathy?

DYT1 dystonia is an autosomal dominant movement disorder, characterized by early onset of involuntary sustained muscle contractions. It is caused by a 3-bp deletion in the DYT1 gene, which results in the deletion of a single glutamate residue in the C-terminus of the protein TA (torsinA). TA is a member of the AAA+ (ATPase associated with various cellular activities) family of chaperones with multiple functions in the cell. There is no evidence of neurodegeneration in DYT1 dystonia, which suggests that mutant TA leads to functional neuronal abnormalities, leading to dystonic movements. In recent years, different functional roles have been attributed to TA, including being a component of the cytoskeleton and the NE (nuclear envelope), and involvement in the secretory pathway and SV (synaptic vesicle) machinery. The aim of the present review is to summarize these findings and the different models proposed, which have contributed to our current understanding of the function of TA, and also to discuss the evidence implicating TA in SV function.