Parkinson's Disease Gene Screening in Familial Cases from Central and South America.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease following Alzheimer's disease. Nearly 30 causative genes have been identified for PD and related disorders. However, most of these genes were identified in European-derived families, and little is known about their role in Latin American populations. OBJECTIVES: Our goal was to assess the spectrum and frequency of pathogenic variants in known PD genes in familial PD patients from Latin America. METHODS: We selected 335 PD patients with a family history of PD from the Latin American Research Consortium on the Genetics of PD. We capture-sequenced the coding regions of 26 genes related to neurodegenerative parkinsonism. Of the 335 PD patients, 324 had sufficient sequencing coverage to be analyzed. RESULTS: We identified pathogenic variants in 41 individuals (12.7%) in FBXO7, GCH1, LRRK2, PARK7, PINK1, PLA2G6, PRKN, SNCA, and TARDBP, GBA1 risk variants in 25 individuals (7.7%), and variants of uncertain significance in another 24 individuals (7.4%) in ATP13A2, ATP1A3, DNAJC13, DNAJC6, GBA1, LRKK2, PINK1, VPS13C, and VPS35. Of the 70 unique variants identified, 19 were more frequent in Latin Americans than in any other population. CONCLUSIONS: This is the first screening of known PD genes in a large cohort of patients with familial PD from Latin America. There were substantial differences in the spectrum of variants observed in comparison to previous findings from PD families of European origin. Our data provide further evidence that differences exist between the genetic architecture of PD in Latinos and European-derived populations. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Adherence to treatment in Parkinson's disease: A multicenter exploratory study with patients from six Latin American countries.

BACKGROUND: Adherence to treatment in Parkinson's disease (PD) is compromised due to the need for multiple therapies, comorbidities related to aging, and the complexity of therapeutic schemes. In the present study, we aimed to explore adherence to treatment in groups of PD patients from six Latin-American (LA) countries and identify its associated demographic and clinical parameters. METHODS: A multicenter, cross-sectional, exploratory study was conducted from September 2016 to March 2017. Treatment adherence was assessed using the simplified medication adherence questionnaire (SMAQ), applied to patients and caregivers. Sociodemographic and clinical variables (MDS-UPDRS Part III-IV, MMSE, Beck Depression Inventory-II (BDI-II)) were recorded. RESULTS: Eight hundred patients from six LA countries were evaluated. Nonadherence was reported in 58.25% of the population, according to patients. The most frequent issues were forgetfulness and correct timing of doses. A high level of agreement in adherence prevalence and most SMAQ items were observed between patients and their caregivers. The nonadherent population had a significantly higher proportion of unemployment, free access to medication, troublesome dyskinesias and off-periods, lesser years of education, and worse motor, cognitive, and mood scores. In multiple logistic and linear regression analyses, MDS-UPDRS Part III, BDI-II, gender, free access to medication, treatment with dopamine agonists alone, years of education, excessive concerns about adverse effects, and beliefs about being well-treated remained significant contributors to adherence measures. CONCLUSION: Educational strategies, greater involvement of PD patients in decision-making, and consideration of their beliefs and values might be of great need to improve medication adherence in this PD population.

Successful Unilateral Surgical Approach to Internal Globus Pallidus and Ventral Intermediate Nucleus of the Thalamus in 3 Cases of Myoclonus-Dystonia Syndrome.

Surgical approaches of internal globus pallidus (GPi) and ventral intermediate thalamic nucleus (Vim) have been used to treat different movement disorders. Three subjects with myoclonus-dystonia syndrome were surgically treated, one of them with GPi and Vim stimulation, while radiofrequency ablation of these structures was performed in the other 2 subjects. Surgical approach of both targets was performed simultaneously on each subject. Mean follow-up was of 33.3 months (22-48 months), the Unified Myoclonus Rating Scale action myoclonus (AM), functional tests (FT), patient questionnaire (PQ) sub-scores, and the Unified Dystonia Rating Scale (UDRS) were used during assessments. Improvement in all scales were seen 6 months after surgery (AM: 74%, FT: 60%, PQ: 63%, UDRS: 65%), and this benefit persisted throughout follow-up (AM: 61%, FT:62%, PQ: 65%, UDRS: 86%). No adverse events were noticed. Simultaneous unilateral procedures of GPi and Vim by either stimulation or ablation techniques improve both motor and functional scores in myoclonus-dystonia syndrome.

Cannabis in patients with Parkinson's disease in Argentina. A cross sectional study.

We made an observational cross-sectional study to evaluate the prevalence of cannabis use, characteristics and results perceived by a group of PD patients. Semi-structured questionnaire was applied to patients. Until obtaining more information we suggest to incorporate into regular medical practice the question about the use of cannabis.

Blepharospasm as a Manifestation of Peak of Dose Dyskinesia in Parkinson Disease.

OBJECTIVES: The aim of the study was to report 4 patients with Parkinson disease (PD) and On-period blepharospasm (BS). METHODS: We analyzed patients with PD and motor fluctuations who developed BS in several different centers in Latin America. RESULTS: Four patients had BS while in the ON periods. CONCLUSIONS: Blepharospasm in the On period in patients with PD is extremely uncommon, and our series is the only one to describe such association.

Weight Loss in Parkinson's Disease: The Relationship with Motor Symptoms and Disease Progression.

OBJECTIVES: To determine the prevalence of weight loss (WL) in PD patients, its relationship to the severity of motor manifestations and appetite changes. METHODS: 144 PD patients and 120 controls were evaluated in a single session. All subjects were asked about changes in body weight and appetite. PD patients were examined with the UPDRS-III and the Hoehn and Yahr (HY) scales. Subscores of tremor, bradykinesia /rigidity, and non-dopaminergic symptoms (NDS) were analyzed individually. Multivariable logistic regression analysis was used to determine an association between WL and PD motor manifestations. RESULTS: 48.6 % of PD patients presented WL compared to 20.8 % of controls (p < 0.001). Weight losers were significantly older and had longer disease duration, higher scores in HY stages, UPDRS-III, and NDS-subscore. Multivariable logistic regression analysis demonstrated that WL was associated with NDS-subscore (p= 0.002; OR: 1.33) and older age (p= 0.037; OR: 1.05). Appetite in PD cases losing weight was unchanged (35.7 %), decreased (31.4 %), or even increased (32.9). CONCLUSIONS: Our results showed that WL occurs in almost half of PD patients and it is largely the consequence of disease progression rather than involuntary movements or a decrease in food intake.

Erratum: Variable frequency of LRRK2 variants in the Latin American research consortium on the genetics of Parkinson's disease (LARGE-PD), a case of ancestry.

[This corrects the article DOI: 10.1038/s41531-017-0020-6.].

Variable frequency of LRRK2 variants in the Latin American research consortium on the genetics of Parkinson's disease (LARGE-PD), a case of ancestry.

Mutations in Leucine-Rich Repeat Kinase 2 (LRRK2), primarily located in codons G2019 and R1441, represent the most common genetic cause of Parkinson's disease in European-derived populations. However, little is known about the frequency of these mutations in Latin American populations. In addition, a prior study suggested that a LRRK2 polymorphism (p.Q1111H) specific to Latino and Amerindian populations might be a risk factor for Parkinson's disease, but this finding requires replication. We screened 1734 Parkinson's disease patients and 1097 controls enrolled in the Latin American Research Consortium on the Genetics of Parkinson's disease (LARGE-PD), which includes sites in Argentina, Brazil, Colombia, Ecuador, Peru, and Uruguay. Genotypes were determined by TaqMan assay (p.G2019S and p.Q1111H) or by sequencing of exon 31 (p.R1441C/G/H/S). Admixture proportion was determined using a panel of 29 ancestry informative markers. We identified a total of 29 Parkinson's disease patients (1.7%) who carried p.G2019S and the frequency ranged from 0.2% in Peru to 4.2% in Uruguay. Only two Parkinson's disease patients carried p.R1441G and one patient carried p.R1441C. There was no significant difference in the frequency of p.Q1111H in patients (3.8%) compared to controls (3.1%; OR 1.02, p = 0.873). The frequency of LRRK2-p.G2019S varied greatly between different Latin American countries and was directly correlated with the amount of European ancestry observed. p.R1441G is rare in Latin America despite the large genetic contribution made by settlers from Spain, where the mutation is relatively common.

A Multicenter Comparative Study of Impulse Control Disorder in Latin American Patients With Parkinson Disease.

OBJECTIVES: Impulse control disorder (ICD) is a common adverse effect in patients with Parkinson disease who receive dopamine agonists; however, other factors are involved in its manifestations. To study the frequency and factors involved in the development of this adverse effect in a Latin American population, we conducted a cross-sectional multicenter study. METHODS: Two hundred fifty-five patients in 3 Latin American centers were evaluated by examination and application of scales (Unified Parkinson's Disease Rating Scale, Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale, Hoehn and Yahr, Clinical Impression of Severity Index for Parkinson's Disease). RESULTS: Of the patients, 27.4% had ICD, most of whom were on dopamine agonists. Other associated risk factors included a younger age at onset of Parkinson disease, moderate symptoms, a shorter evolution of the clinical manifestations, rapid eye movement (REM) sleep disorder behavior, and the consumption of tea, mate, and alcohol. CONCLUSIONS: The frequency of ICD is higher in Latin America than in Anglo-Saxon populations. Consuming tea and mate, in addition to the use of dopamine agonists, is a factor that may demonstrate a genetic link that predisposes patients to the establishment of an ICD.

Alcohol-Sensitive Generalized Dystonia.

We report the case of a 29-year-old male patient with a generalized and progressive dystonia that led him unable to stand. Multiple antidystonic treatments were tried without benefit. Alcohol test was positive with a dramatic improvement. To the best of our knowledge, this is the first reported case of generalized dystonia without other clinical manifestations sensitive to alcohol.

Paroxysmal Nonkinesigenic Dyskinesias Responsive to Carbamazepine in Fahr Syndrome: A Case Report.

OBJECTIVE: This study aimed to report the case of a patient with paroxysmal nonkinesigenic dyskinesias and Fahr syndrome who had a marked response to carbamazepine. METHODS: We present the case of a 57-year-old female patient with episodes of paroxysmal choreoathetoid dyskinesias in the oromandibular region and distal region of upper and lower extremities, with fluctuating dystonic postures in the same distribution; duration was variable ranging from 30 minutes to 3 hours. Laboratory studies were consistent with primary hyperparathyroidism with bilateral brain calcifications. RESULTS: Treatment with low doses of carbamazepine was successful.

[Community acquired bacterial meningitis in patients over 60]. / Meningitis bacteriana adquirida en la comunidad en mayores de 60 años.

Acute bacterial meningitis has a global mortality rate of 135000 cases per year. In Argentina over the last 12 years, the annual incidence rate has been 5.5/100 000. About 20% of patients present neurological sequelae, which are more common in patients aged 60 or older. Our objective here is to determine the clinical characteristics, the most common causes and to measure evolution in patients over 60 years old diagnosed with meningitis and treated at the Hospital de Clinicas José de San Martín. This is a retrospective study based on a review of medical records from 2003 to 2013 that takes into account patients older than 60 who were diagnosed with acute bacterial meningitis acquired in the community by a microbiological diagnosis of CSF or those included due to a high suspicion of bacterial meningitis (pleocitosis > 2000 cells/mm3, proteins > 220 mg/dl, glycorrhachia < 34 mg/dl, glycorrhachia/glucose index < 0.23). Cases of TB meningitis, nosocomial, postoperative and other nonbacterial meningitis were excluded. Sixty nine patients were included, 45 (65%) were women with an average age of 78 ± 10.6 years. Only 40% had the triad of classical meningitis symptoms (stiff neck, fever and altered mental status). In 52% of the patients germs developed in the CSF, the most frequent being Streptococcus pneumoniae present in 47% of cases. Lethality rate was 41%, all of them by methicillin-sensitive Staphylococcus aureus. Only 24 (35%) cases were admitted into intensive care. The main sequelae present were motor disorders (12%) and hearing loss (5%).

Recurrent and Alternating Pisa Syndrome.

OBJECTIVES: The aims of the study were to report the case of a male patient who developed a first episode of Pisa syndrome (PS) to the right side and a second episode to the left side and to discuss the hypothesis that states that denervation is one of the main mechanisms implicated in the development of PS. METHODS: We report on the case of a 71-year-old patient with Parkinson disease who developed PS to the right side while on dopaminergic treatment with pramipexol and levodopa. The dopamine agonist was discontinued and the postural abnormality was corrected increasing the levodopa dose. Six years later, while on ropinirole and levodopa, he developed PS again but this time the lean was to the left. Even though the dopamine agonist was discontinued, this condition failed to improve. CONCLUSIONS: Mechanisms other than denervation and its relationship with the more or less affected side contribute to the development of the syndrome.This is the first report of a case of recurrent alternating PS and highlights the need for research on this topic to better understand this disorder.

Handwriting Rehabilitation in Parkinson Disease: A Pilot Study.

OBJECTIVE: To assess the utility of handwriting rehabilitation (HR) in Parkinson disease (PD) patients who experienced difficulties with handwriting and signing. METHODS: Sixty PD patients were prospectively studied with graphological evaluations. Thirty PD patients were assigned to HR for 9 weeks. At the end of this training, all patients were evaluated again and results of basal vs. final evaluations were compared. RESULTS: At final evaluation, the group assigned to HR showed significantly larger amplitude of the first 'e' in the phrase, larger signature surface area, and superior margin. A trend of increase in letter size was also observed. Handwriting with progressively decreasing size of letters and ascending direction with respect to the horizontal were prominent findings in both groups of patients and they did not change after HR. CONCLUSION: Rehabilitation programs for handwriting problems in PD patients are likely to be helpful. Larger randomized studies are needed to confirm these results.

Pisa Syndrome.

Lateral trunk flexion is often seen in patients with Parkinson disease, sometimes coming on as a subacute phenomenon associated with medication adjustments, and in others with gradual onset that seems related to a neurodegenerative process related to the evolution of the disease.Either acute or subacute presentations seem to be pure abnormalities in the coronal plane and are usually reversible. However, a chronic form occurs often in a combined fashion with anteroposterior flexion (camptocormia), improves only partially, remains stable, or even worsens over time.The acute/subacute phenotype is the condition originally named as Pisa syndrome (PS).The pathophysiology of PS remains poorly understood, and a cholinergic-dopaminergic imbalance has been suggested as being involved in the cause of this disorder. The role of other neurotransmitters and how they become dysfunctional in PS remains to be elucidated.Specific treatments, other than discontinuing the medications responsible for the disorder, whenever possible, are undeveloped because of the unknown etiology.