Daniel Teixeira-Dos-Santos

Late-onset progressive hemiparkinsonism may emerge years or even decades after an acute midbrain insult, such as hemorrhage secondary to a cavernous malformation. Two complementary hypotheses may explain this delayed onset: an initial loss of dopaminergic neurons in the substantia nigra, with surviving neurons compensating for striatal function until age-related decline reaches the clinical threshold, and a delayed neurodegenerative process, such as trans-synaptic degeneration of the substantia nigra following striatal injury. Although post-midbrain lesion parkinsonism may mimic Parkinson’s disease and initially respond dramatically to low-dose levodopa, these patients have an increased risk of motor fluctuations and levodopa-induced dyskinesias. While approximately 50% of patients with idiopathic Parkinson’s disease develop dyskinesias within 5 years, those with acute midbrain injury may develop wearing-off and peak-dose dyskinesias within the first year of levodopa therapy. This rapid onset likely results from severe pre-existing nigral denervation combined with chronic pulsatile dopaminergic stimulation due to levodopa’s short half-life. Clinically, the focal and unilateral nature of the brainstem cavernoma results in asymmetric dyskinesias and dystonia, predominantly affecting the hemibody most involved in the initial parkinsonism. Pharmacological management of dyskinesias without worsening parkinsonian symptoms includes levodopa dose fractionation, addition of dopaminergic agonists to reduce pulsatile stimulation, and amantadine, an NMDA receptor antagonist that reduces striatal glutamatergic hyperactivity involved in levodopa-induced dyskinesias and may decrease dyskinesia duration by up to 60% without compromising motor benefit. In cases refractory to pharmacological treatment, surgical options may be considered to control dyskinesias, including unilateral pallidotomy and deep brain stimulation targeting the subthalamic nucleus or internal globus pallidus.

The genetics of Parkinson’s disease (PD) in underrepresented populations remain poorly characterized, potentially overlooking population-specific contributions. We analyzed 461 Chilean PD cases from a movement disorders center. Pathogenic, likely pathogenic, or GBA1 risk variants were identified in 58 individuals (12.6%), mainly in LRRK2 (50%) and GBA1 (44.8%), while PRKN, SNCA , and SQSTM1 collectively represented 5.2%. All LRRK2 variants were p.G2019S, with an overall frequency of 6.3%, the highest reported in South America, and enrichment of Ashkenazi Jewish ancestry at this locus. These findings characterize the genetic landscape of PD in Chile and support its relevance for LRRK2 -targeted studies.

Background: Evidence on environmental determinants of Parkinson’s disease (PD) in Latin America is limited and their attributable burden remains poorly defined in the region. We examined associations between environmental exposures and PD and quantified their contribution to disease burden.Methods: We analyzed 9887 participants from nine Latin American countries in a case control study. Associations between environmental exposures and PD were estimated using logistic regression adjusted for age, sex, and country. Population attributable fractions (PAFs) were calculated for positively associated exposures, defined as severe head trauma or at least 5 years of exposure for other risk factors.Findings: Weekly caffeine consumption and tobacco use for at least 5 years were inversely associated with PD (adjusted OR [aOR] 0·77, p < 0·0001; aOR 0·83, p = 0·0009). Severe head trauma (aOR 1·35, p < 0·0001), occupational pesticide exposure (aOR 1·42, p = 0·0003), occupational metal exposure (aOR 1·29, p = 0·0299), rural living (aOR 1·60, p < 0·0001), and well water consumption (aOR 1·22, p = 0·0014) were positively associated with PD. Dose related associations were observed for caffeine, tobacco, occupational pesticides and metals, rural living, and well water consumption. The joint PAF across five risk exposures was 13·7% (95% CI 9·8 to 17·3), with higher estimates in El Salvador, Brazil, Colombia, males, and participants younger than 60 years. Sensitivity and lag analyses were directionally consistent.Interpretation: Selected environmental exposures may account for a meaningful proportion of PD burden in Latin America, supporting further research and public health attention to environmental determinants in the region.

Deep brain stimulation (DBS) is an established surgical therapy for advanced Parkinson's disease (PD), but, in Latin America, access remains restricted, and local data are limited. To describe the demographic, clinical, and procedural profile, as well as the treatment outcomes and perioperative complications, of patients undergoing DBS at a Brazilian reference center. We conducted a retrospective observational study including 101 patients with PD who underwent bilateral DBS implantation between 2012 and 2024 at Hospital de Clínicas de Porto Alegre, Brazil, within the public healthcare system. The mean age at surgery was of 62.2 years; 63.4% of the patients were male. The mean ages at symptom onset, diagnosis, DBS indication, and surgery were of 43.1, 45.7, 54.5, and 56.7 years respectively. On average, the patients presented 10.9 years of disease duration when surgery was performed. Motor fluctuations (53.5%) and dyskinesias (41.6%) were the most common indications. The subthalamic nucleus (STN) was the predominant target (97%). Mild complications included wound infection (7.9%), while severe complications, such as lead migration, intracranial hemorrhage, or deep infection occurred in 6.9%. Levodopa equivalent daily dose (LEDD) was the primary outcome used to assess postoperative change; it was significantly reduced by ∼ 25% after DBS, from 1,885.6 to 1,406.7 mg at 12 months (Wilcoxon p < 0.001). In the cohort of the present study, DBS was safe and enabled a sustained reduction in dopaminergic medication during follow-up. Despite these benefits, delays in surgery, limited access through the public health system, and device-availability issues continue to limit broader implementation, highlighting persistent structural inequalities in Latin America.

Background: Although levodopa is the gold standard treatment for Parkinson's disease (PD), its chronic use is associated with levodopa-induced dyskinesia (LID), a motor complication that impacts prognosis, quality of life, and treatment costs. Most known LID-associated factors have been identified in European-descendant populations. Objectives: To describe the epidemiology of LID in Latin American and Caribbean (LATAM) countries and assess the relevance of known and novel LID-associated factors in this population. Methods: We conducted a cross-sectional study using data from the Latin American Research consortium on the Genetics of Parkinson's Disease (LARGE-PD). We included PD patients with information on LID status and levodopa use from eight LATAM countries. LID prevalence was calculated overall and by country. Countries were compared on demographic and clinical variables. Logistic regression was used to identify associations with LID. Results: A total of 3695 PD patients (58.8% male) were included. Overall LID prevalence was 25.4% [95% CI: 24.06–26.87], ranging from 9.3% in Colombia to 45.1% in Puerto Rico. Prevalence increased progressively with longer disease duration. Country comparisons showed that not all known LID-associated factors explained prevalence differences. In logistic regression, fast disease progression was significantly associated with LID (OR: 1.55, 95%CI: 1.16–2.07), while sex was not (OR: 1.02, 95%CI: 0.87–1.18). Conclusions: This is the largest study on LID epidemiology in LATAM. While some known risk factors remain relevant, others, like sex, do not, underscoring the need for population-specific studies. Future work should integrate environmental, clinical, and genetic data to better understand LID mechanisms.