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.

Impulsivity Markers in Parkinsonian Subthalamic Single-Unit Activity.

BACKGROUND: Impulsive-compulsive behaviors are common in Parkinson's disease (PD) patients. However, the basal ganglia dysfunctions associated with high impulsivity have not been fully characterized. The objective of this study was to identify the features associated with impulsive-compulsive behaviors in single neurons of the subthalamic nucleus (STN). METHODS: We compared temporal and spectral features of 412 subthalamic neurons from 12 PD patients with impulsive-compulsive behaviors and 330 neurons from 12 PD patients without. Single-unit activities were extracted from exploratory microrecordings performed during deep brain stimulation (DBS) implant surgery in an OFF medication state. RESULTS: Patients with impulsive-compulsive behaviors displayed decreased firing frequency during bursts and a larger fraction of tonic neurons combined with weaker beta coherence. Information carried by these features led to the identification of patients with impulsive-compulsive behaviors with an accuracy greater than 80%. CONCLUSIONS: Impulsive-compulsive behaviors in PD patients are associated with decreased bursts in STN neurons in the OFF medication state. © 2021 International Parkinson and Movement Disorder Society.

Consensus guidelines for botulinum toxin therapy: general algorithms and dosing tables for dystonia and spasticity.

Botulinum toxin (BT) therapy is a complex and highly individualised therapy defined by treatment algorithms and injection schemes describing its target muscles and their dosing. Various consensus guidelines have tried to standardise and to improve BT therapy. We wanted to update and improve consensus guidelines by: (1) Acknowledging recent advances of treatment algorithms. (2) Basing dosing tables on statistical analyses of real-life treatment data of 1831 BT injections in 36 different target muscles in 420 dystonia patients and 1593 BT injections in 31 different target muscles in 240 spasticity patients. (3) Providing more detailed dosing data including typical doses, dose variabilities, and dosing limits. (4) Including total doses and target muscle selections for typical clinical entities thus adapting dosing to different aetiologies and pathophysiologies. (5) In addition, providing a brief and concise review of the clinical entity treated together with general principles of its BT therapy. For this, we collaborated with IAB-Interdisciplinary Working Group for Movement Disorders which invited an international panel of experts for the support.

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.

Strategies for treatment of dystonia.

Treatment of dystonias is generally symptomatic. To produce sufficient therapy effects, therefore, frequently a multimodal and interdisciplinary therapeutic approach becomes necessary, combining botulinum toxin therapy, deep brain stimulation, oral antidystonic drugs, adjuvant drugs and rehabilitation therapy including physiotherapy, occupational therapy, re-training, speech therapy, psychotherapy and sociotherapy. This review presents the recommendations of the IAB-Interdisciplinary Working Group for Movement Disorders Special Task Force on Interdisciplinary Treatment of Dystonia. It reviews the different therapeutic modalities and outlines a strategy to adapt them to the dystonia localisation and severity of the individual patient. Hints to emerging and future therapies will be given.

Remarkable clinical improvement with bilateral globus pallidus internus deep brain stimulation in a case of Lesch-Nyhan disease: five-year follow-up.

OBJECTIVES: Lesch-Nyhan disease (LND) is a hereditary disorder characterized by hyperuricemia, self-mutilation, developmental retardation, and movement disorders such as spasticity and dystonia. The lack of a precise understanding of the neurological dysfunction has precluded the development of useful conservative therapies. We present our experience treating a LND patient by bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) with improvement in dystonia symptoms and disappearance of self-injurious behavior. METHODS: We present a 29-year-old patient characterized by generalized severe dystonia and self-injurious behavior, both refractory to conservative treatment. The patient underwent a GPi bilateral electrode implant for chronic stimulation. Symptoms were evaluated with the Burke-Fhan-Marsden Dystonia Rating Scale (BFMDRS) and Mean Disability Scale (MDS) preoperatively and during the five-year follow-up. RESULTS: We observed a remarkable improvement in dystonia symptoms and complete disappearance of self-injurious behavior. CONCLUSIONS: This case supports the hypothesis that automutilation in LND might be related to dysfunction of the basal ganglia circuits and the idea that bilateral GPi-DBS is a safe and effective treatment modality for this condition.

[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%).

Analysis of D216H polymorphism in Argentinean patients with primary dystonia.

The D216H polymorphism (rs1801968) in TOR1A has been suggested as a risk factor for developing primary dystonia in German subjects not carrying the deletion c.904-906delGAG (∆GAG). However, this association could not be confirmed in other populations with different ethnic backgrounds. The purpose of this study is to evaluate the D216H polymorphism in an Argentinean cohort of 40 patients with primary dystonia and 200 unrelated control subjects. The authors could observe a significantly higher frequency of the H216 variant in dystonic patients lacking ∆GAG as compared with controls.

Behavioral and motor improvement after deep brain stimulation of the globus pallidus externus in a case of Tourette's syndrome.

OBJECTIVES: The objective of our paper is to show the partial decrease of therapeutic effect with battery exhaustion in a previously successfully treated patient with refractory Tourette's syndrome (TS). MATERIALS AND METHODS: We present a 47-year-old patient diagnosed with TS based on the TS Study Group Criteria and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Surgery was considered based on refractoriness to conservative management. Presurgical evaluation included magnetic resonance imaging (MRI), positron emission tomography scan, and neuropsychologic, neurologic, and psychiatric tests utilizing Yale Brown Obsessive Compulsive Scale, Yale Global Tics Severity Scale, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Global Assessment of Functioning Scale, and Mini-mental State Examination. Target coordinates were obtained from inversion recovery MRI. Quadripolar deep brain stimulation (DBS) electrodes were implanted bilaterally in the globus pallidus externus (GPe) and connected to the pulse generator in the same procedure. To determine the clinical response to DBS, the scores of the scales obtained preoperatively were compared with those obtained postoperatively. RESULTS: No surgical complications were detected and according to the clinical scales the patient experienced a marked improvement of his symptoms, although he never showed obsessive-compulsive disorder components of any type. The battery was exhausted after two years with the subsequent significant partial loss of therapeutic effect. CONCLUSIONS: GPe seems to be a highly promising target of DBS for the treatment of medically refractory TS. After battery exhaustion, the patient experienced a marked partial decrease in the therapeutic effect, which confirms the beneficial action of this method.

Perampanel, an AMPA antagonist, found to have no benefit in reducing "off" time in Parkinson's disease.

BACKGROUND: Perampanel is a selective, noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor antagonist. Two multicenter randomized, double-blind, placebo-controlled, parallel-group phase III studies assessed the efficacy and safety of adjunctive perampanel in patients with Parkinson's disease and motor fluctuations. METHODS: In both phase III studies (301 and 302), levodopa-treated patients were randomized and treated with once-daily oral placebo (n = 504), perampanel 2 mg (n = 509), or perampanel 4 mg (n = 501). The primary end point was change in daily "off" time from baseline. The treatment period was 30 weeks in study 301 and 20 weeks in study 302. RESULTS: For any efficacy end point, perampanel 2 or 4 mg was not superior to placebo. Perampanel was well tolerated up to 4 mg/day. CONCLUSIONS: Perampanel failed to significantly improve motor symptoms versus placebo. There was also no effect on the duration or disability of levodopa-induced dyskinesia.

Impulsivity is associated with firing regularity in parkinsonian ventral subthalamic nucleus.

Impulsive-compulsive behaviors (ICB) are over-represented in Parkinson's disease (PD) patients. Neurons in the ventral subthalamic nucleus (STN) might play a predominant role in the modulation of impulsivity. We characterized the firing regularity of 742 subthalamic neurons from 24 PD patients (12 ICB+ and 12 ICB-) in an OFF medication state. We computed the firing regularity in the dorsal and ventral STN regions, and we compared their performance in discriminating ICB patients. Regularity of ventral neurons in ICB+ patients is higher and supports a significant discrimination between the two cohorts. These results substantiate a ventral location of neurons involved in impulsivity.

Yerbamate Tea Consumption: A Protective Factor in Parkinson Disease.

INTRODUCTION: Little is known about the association between Yerbamate (YMT) tea consumption and Parkinson disease (PD). We determined whether there was an association between YMT tea consumption and PD. METHODS: We conducted a multicenter case-control study in 3 countries (Argentina, Paraguay, and Uruguay). We applied a structured questionnaire about YMT tea consumption history. The survey also included information about factors previously associated with a decreased and increased risk of PD, apart from medical and demographic factors. Odds ratios and 95% confidence intervals were calculated using multivariate unconditional binary logistic regression analysis. RESULTS: We included 215 cases and 219 controls. The mean age of the cases was 65.6 ± 10.5 years and that of controls was 63.1 ± 10.5 years (P < 0.02). Years of YMT tea consumption, number of liters drunk per day, and amount of YMT used for preparing the infusion were similar between cases and controls (P > 0.05), but not the number of times the YMT was added into the container (P = 0.003) and the YMT tea concentration per serving (P = 0.02). The multivariate analysis showed that YMT tea concentration per serving lowered the risk for PD, independent of potential confounders (odds ratio, 0.62; 95% confidence interval, 0.47-0.84). CONCLUSIONS: This multicenter study highlights the association between an environmental factor, the YMT tea drinking, and PD. Although more evidence from longitudinal studies is needed, the results obtained here points toward a protective effect of the YMT tea concentration per serving on PD.

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.

Use of complementary and alternative therapies in outpatients with Parkinson's disease in Argentina.

We interviewed 300 patients (54.7% male; mean age was 65.8 ± 9.5) attending the Movement Disorders Clinic at the Buenos Aires University Hospital to determine the prevalence of CATs use and their association with demographic, social, or disease-specific characteristics among patients with Parkinson's disease (PD) in Buenos Aires, Argentina. We found that 25.7% of the PD patients interviewed (77/300) stated they had used CATs to improve their PD symptoms whereas 38.0% (114/300) had used some CATs without any relation to PD, at least once in life. At the moment of the interview, CATs prevalence use was 50.6% in the former group and 25.0% in the latter. The use of CATs was much more frequent among women and more common in the 50- to 69-year age group. Friends and neighbors of the patients had most frequently recommended these therapies. No major association was observed between CATs use and the duration of the disease, side of initial involvement, PD phenotype, or the Hoehn and Yahr staging. Acupuncture, homeopathy, yoga, and therapeutic massage were the most widely used therapies. After the initiation of conventional treatment the use of massage, yoga, and acupuncture in patients using CATs to improve PD significantly increased. Neurologists should be aware and inquire about the use of CATs to rule out potentially harmful effects.

Cross-cultural evaluation of the modified Parkinson Psychosis Rating Scale across disease stages.

This study assessed the psychometric attributes of the modified Parkinson Psychosis Rating Scale (mPPRS). In an attempt to improve scale's scaling assumptions and content validity, all types of hallucinations were rated and all items were scored based on intensity. The scale was cross-culturally adapted to four Latin American countries (Argentina, Brazil, Ecuador, and Paraguay). Acceptability, internal consistency, factor structure, convergent and known-groups validity, and precision (standard error of measurement, SEM) were explored. A total of 388 patients with PD were included in the study (age, 64.5 +/- 10.7 years; 59.8% males; PD duration, 8.2 +/- 4.9 years). The mPPRS was highly usable in terms of missing values generated and scores distribution (total computable scores, 99.7%, ceiling effect, <15%). Scaling assumptions were acceptable as noted by the range of item-total correlations (0.14-0.55, only one coefficient below 0.2). Internal consistency was adequate for research use (Cronbach alpha, 0.7). Factor analysis identified two factors that accounted for 58.5% of the variance. Low correlation coefficients were found with cognitive function (SCOPA-Cog) and disease severity (CISI-PD) (r(S)

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.

Cognitive disturbances in primary blepharospasm.

The common belief that primary dystonia is a purely motor disorder with no anatomical substrate and no other accompanying neurological dysfunction has recently been challenged. In addition, there is increasing evidence that the basal ganglia besides motor control, plays a role in cognitive functioning. However, no systematic cognitive performance evaluation has been carried out in patients with primary blepharospasm (BS), one of the most common forms of adult dystonia. We evaluated a series of 20 patients with primary BS and a group of 17 controls matched by severity of mood symptoms, age, and sex. BS patients performed significantly worse on the Luria sequencing test, Purdue pegboard test, reciprocal coordination, tactile denomination, and reverse visuospatial span and the differences persisted after correction for age, duration of disease, severity of BS, and degree of depression. The Wisconsin card sorting test showed no statistical difference, but BS patients made more errors and more perseverative answers than expected according to population means, whereas the control group performed poorly but within normal parameters. Our findings suggest broad cortical involvement in focal dystonia that is not correlated with the severity or duration of dystonia.