Neuroprotective Effects Exerted by a Combination of Selected Lactic Acid Bacteria in a Mouse Parkinsonism Model under Levodopa-Benserazide Treatment.

Alterations of the microbiota-gut-brain axis has been associated with intestinal and neuronal inflammation in Parkinson's disease (PD). The aim of this work was to study some mechanisms associated with the neuroprotective effect of a combination (MIX) of lactic acid bacteria (LAB) composed by Lactiplantibacillus plantarum CRL2130 (riboflavin overproducing strain), Streptococcus thermophilus CRL808 (folate producer strain), and CRL807 (immunomodulatory strain) in cell cultures and in a chronic model of parkinsonism induced with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in aged mice, and under levodopa-benserazide treatment. In vitro, N2a differentiated neurons were exposed to the neurotoxin 1-methyl-4-phenylpyridinium (MPP+) and treated with intracellular bacterial extracts or with conditioned media from BV-2 cells exposed to the bacterial extracts. In vivo, motor skills, tyrosine hydrolase (TH) in brain and cytokine concentrations in serum and in brain were evaluated. The study of the faecal microbiota and the histology of the small intestine was also performed. The results showed that the neuroprotective effect associated with LAB MIX administration did not interfere with levodopa-benserazide treatment. This effect could be associated with the antioxidant and immunomodulatory potential of the LAB selected in the MIX, and was associated with the significant improvement in the motor tests and a higher number of TH + cells in the brain. In addition, LAB MIX administration was associated with modulation of the immune response. LAB administration decreased intestinal damage with an increase in the villus length /crypt depth ratio. Finally, the administration of the LAB MIX in combination with levodopa-benserazide treatment was able to partially revert the intestinal dysbiosis observed in the model, showing greater similarity to the profiles of healthy controls, and highlighting the increase in the Lactobacillaceae family. Different mechanisms of action would be related to the protective effect of the selected LAB combination which has the potential to be evaluated as an adjuvant for conventional PD therapies.

First family with Perry syndrome from Mexico.

Perry syndrome (PS) is a rare autosomal dominant disease characterized by parkinsonism, central hypoventilation, weight loss and depression and is caused by pathogenic mutations in the dynactin subunit 1 (DCTN1) gene (encoding p150glued protein). To date, only two cases have been reported in Latin America, specifically in Colombia and Argentina. The present study, to the best of our knowledge, reports the first recorded Mexican family with PS. The clinical features of the proband and a family history of early parkinsonism led to the suspicion of PS. The pathogenic variant NM_004082:c.212G>A, causing a (p.Gly71Glu) mutation in the p150glued protein, was identified in exon 2 of the DCTN1 gene by exome sequencing, confirming the diagnosis of PS. (p.Gly71Glu) has been previously identified in at least 4 cases of PS from different ethnic backgrounds. Genetic counseling was provided to the available family members. To clarify the impact of the (p.Gly71Glu) variant on the structure and function of the cytoskeleton-associated protein Gly rich (CAP-Gly) domain of p150glued, Glu71 mutated CAP-Gly domains were modeled and compared with the wild-type. It was hypothesized that the larger and more charged side chain of Glu may induce conformational and electrostatic changes, imposing a conformational restriction on the peptide backbone that would affect interaction with the p150glued protein partners, causing dysfunction in the dynactin protein complex.

Omega-3 polyunsaturated fatty acids and Parkinson's disease: A systematic review of animal studies.

Parkinson's disease (PD) is the second most common neurodegenerative disorder. The primary pathological features of PD include the presence of α-synuclein aggregates and Lewy bodies, mitochondrial dysfunction, oxidative stress, and neuroinflammation. Recently, omega-3 fatty acids (ω-3 PUFAs) have been under investigation as a preventive and/or therapeutic strategy for PD, primarily owing to their antioxidant and anti-inflammatory properties. Therefore, the objective of this study was to conduct a systematic review of the literature, focusing on studies that assessed the effects of ω-3 PUFAs in rodent models mimicking human PD. The search was performed using the terms "Parkinson's disease," "fish oil," "omega 3," "docosahexaenoic acid," and "eicosapentaenoic acid" across databases PUBMED, Web of Science, Science Direct, Scielo, and Google Scholar. Following analysis based on predefined inclusion and exclusion criteria, 39 studies were included. Considering behavioral parameters, pathological markers of the disease, quantification of ω-3 PUFAs in the brain, as well as anti-inflammatory, antioxidant, and anti-apoptotic effects, it can be observed that ω-3 PUFAs exhibit a potential neuroprotective effect in PD. In summary, this systematic review presents significant scientific evidence regarding the effects and mechanisms underlying the neuroprotective properties of ω-3 PUFAs, offering valuable insights for the development of future clinical investigations.

Trans-Spinal Theta Burst Magnetic Stimulation in Parkinson's Disease and Gait Disorders.

BACKGROUND: Gait disorders in patients with Parkinson's disease (PD) can become disabling with disease progression without effective treatment. OBJECTIVES: To investigate the efficacy of intermittent θ burst trans-spinal magnetic stimulation (TsMS) in PD patients with gait and balance disorders. METHODS: This was a randomized, parallel, double-blind, controlled trial. Active or sham TsMS was applied at third thoracic vertebra with 100% of the trans-spinal motor threshold, during 5 consecutive days. Participants were evaluated at baseline, immediately after last session, 1 and 4 weeks after last session. Primary outcome was Total Timed Up and Go (TUG) values comparing active versus sham phases 1 week after intervention. The secondary outcome measurements consisted of motor, gait and balance scales, and questionnaires for quality of life and cognition. RESULTS: Thirty-three patients were included, average age 68.5 (6.4) years in active group and 70.3 (6.3) years in sham group. In active group, Total TUG mean baseline was 107.18 (95% CI, 52.1-116.1), and 1 week after stimulation was 93.0 (95% CI, 50.7-135.3); sham group, Total TUG mean baseline was 101.2 (95% CI, 47.1-155.3) and 1 week after stimulation 75.2 (95% CI 34.0-116.4), P = 0.54. Similarly, intervention had no significant effects on secondary outcome measurements. During stimulation period, five patients presented with mild side effects (three in active group and two in sham group). DISCUSSION: TsMS did not significantly improve gait or balance analysis in patients with PD and gait disorders. The protocol was safe and well tolerated. © 2024 International Parkinson and Movement Disorder Society.

Identification of metabolic pathways and key genes associated with atypical parkinsonism using a systems biology approach.

Atypical parkinsonism (AP) is a group of complex neurodegenerative disorders with marked clinical and pathophysiological heterogeneity. The use of systems biology tools may contribute to the characterization of hub-bottleneck genes, and the identification of its biological pathways to broaden the understanding of the bases of these disorders. A systematic search was performed on the DisGeNET database, which integrates data from expert curated repositories, GWAS catalogues, animal models and the scientific literature. The tools STRING 11.0 and Cytoscape 3.8.2 were used for analysis of protein-protein interaction (PPI) network. The PPI network topography analyses were performed using the CytoHubba 0.1 plugin for Cytoscape. The hub and bottleneck genes were inserted into 4 different sets on the InteractiveVenn. Additional functional enrichment analyses were performed to identify Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology for a described set of genes. The systematic search in the DisGeNET database identified 485 genes involved with Atypical Parkinsonism. Superimposing these genes, we detected a total of 31 hub-bottleneck genes. Moreover, our functional enrichment analyses demonstrated the involvement of these hub-bottleneck genes in 3 major KEGG pathways. We identified 31 highly interconnected hub-bottleneck genes through a systems biology approach, which may play a key role in the pathogenesis of atypical parkinsonism. The functional enrichment analyses showed that these genes are involved in several biological processes and pathways, such as the glial cell development, glial cell activation and cognition, pathways were related to Alzheimer disease and Parkinson disease. As a hypothesis, we highlight as possible key genes for AP the MAPT (microtubule associated protein tau), APOE (apolipoprotein E), SNCA (synuclein alpha) and APP (amyloid beta precursor protein) genes.

X-Linked Levodopa-Responsive Parkinsonism-Epilepsy Syndrome: A Novel PGK1 Mutation and Literature Review.

BACKGROUND: Genetic underpinnings in Parkinson's disease (PD) and parkinsonian syndromes are challenging, and recent discoveries regarding their genetic pathways have led to potential gene-specific treatment trials. CASES: We report 3 X-linked levodopa (l-dopa)-responsive parkinsonism-epilepsy syndrome cases due to a hemizygous variant in the phosphoglycerate kinase 1 (PGK1) gene. The likely pathogenic variant NM_000291.4 (PGK1):c.950G > A;p.(Gly317Asp) was identified in a hemizygous state. LITERATURE REVIEW: Only 8 previous cases have linked this phenotype to PGK1, a gene more commonly associated with hemolytic anemia and myopathy. The unusual association of epilepsy, psychiatric symptoms, action tremor, limb dystonia, cognitive symptoms, and l-dopa-responsive parkinsonism must draw attention to PGK1 mutations, especially because this gene is absent from most commercial hereditary parkinsonism panels. CONCLUSIONS: This report aims to shed light on an overlooked gene that causes hereditary parkinsonian syndromes. Further research regarding genetic pathways in PD may provide a better understanding of its pathophysiology and open possibilities for new disease-modifying trials, such as SNCA, LRRK2, PRKN, PINK1, and DJ-1 genes.

Frequency of Hereditary and GBA1-Related Parkinsonism in Latin America: A Systematic Review and Meta-Analysis.

BACKGROUND: Identifying hereditary parkinsonism is valuable for diagnosis, genetic counseling, patient prioritization in trials, and studying the disease for personalized therapies. However, most studies were conducted in Europeans, and limited data exist on admixed populations like those from Latin America. OBJECTIVES: This study aims to assess the frequency and distribution of genetic parkinsonism in Latin America. METHODS: We conducted a systematic review and meta-analysis of the frequency of parkinsonian syndromes associated with genetic pathogenic variants in Latin America. We defined hereditary parkinsonism as those caused by the genes outlined by the MDS Nomenclature of Genetic Movement Disorders and heterozygous carriers of GBA1 pathogenic variants. A systematic search was conducted in PubMed, Web of Science, Embase, and LILACS in August 2022. Researchers reviewed titles and abstracts, and disagreements were resolved by a third researcher. After this screening, five researchers reanalyzed the selection criteria and extracted information based on the full paper. The frequency for each parkinsonism-related gene was determined by the presence of pathogenic/likely pathogenic variants among screened patients. Cochran's Q and I2 tests were used to quantify heterogeneity. Meta-regression, publication bias tests, and sensitivity analysis regarding study quality were also used for LRRK2-, PRKN-, and GBA1-related papers. RESULTS: We included 73 studies involving 3014 screened studies from 16 countries. Among 7668 Latin American patients, pathogenic variants were found in 19 different genes. The frequency of the pathogenic variants in LRRK2 was 1.38% (95% confidence interval [CI]: 0.52-2.57), PRKN was 1.16% (95% CI: 0.08-3.05), and GBA1 was 4.17% (95% CI: 2.57-6.08). For all meta-analysis, heterogeneity was high and publication bias tests were negative, except for PRKN, which was contradictory. Information on the number of pathogenic variants in the other genes is further presented in the text. CONCLUSIONS: This study provides insights into hereditary and GBA1-related parkinsonism in Latin America. Lower GBA1 frequencies compared to European/North American cohorts may result from limited access to gene sequencing. Further research is vital for regional prevalence understanding, enabling personalized care and therapies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Treatment of Parkinson's disease by deep brain stimulation: a bibliometric analysis

ABSTRACT BACKGROUND: For more than 30 years, deep brain stimulation (DBS) has been a therapeutic tool for Parkinson's disease (PD) treatment. DBS can ameliorate several motor and non-motor symptoms and improve the patients' quality of life. OBJECTIVES: To analyze the global scientific production of original and review articles on Parkinson's disease treatment using deep brain stimulation. DESIGN AND SETTING: Descriptive, bibliometric study with a quantitative approach. METHOD: The research protocol was conducted in March 2023 using the Web of Science database. Six hundred eighty-four articles were included in the analysis. Data were imported into RStudio Desktop Software, linked to R Software. The Bibliometrix R package, its Biblioshiny web interface, and VOSviewer software were used for the analysis. RESULTS: The international production began in 1998. Movement Disorders is the journal with the largest number of published articles and the most cited. Michael Okun and Andres Lozano are the authors who produced the most in this area. The University of Florida is the most active affiliated institution in Brazil. The United States has the largest number of collaborations and is mainly published by local researchers. In contrast, countries such as the United Kingdom and Canada have a high number of multi-country publications. The 15 most cited studies predominantly investigated subthalamic nucleus stimulation. CONCLUSION: DBS for Parkinson's disease is a relatively novel therapeutic approach, with studies that have expanded over the last twenty-five years. Most scientific production was quantitative and restricted to specialized journals. The United States, Europe, and China held the most articles.

The clinical diagnosis of Parkinson's disease / O diagnóstico clínico da doença de Parkinson

Abstract After more than 200 years since its initial description, the clinical diagnosis of Parkinson's disease (PD) remains an often-challenging endeavor, with broad implications that are fundamental for clinical management. Despite major developments in understanding it's pathogenesis, pathological landmarks, non-motor features and potential paraclinical clues, the most accepted diagnostic criteria remain solidly based on a combination of clinical signs. Here, we review this process, discussing its history, clinical criteria, differential diagnoses, ancillary diagnostic testing, and the role of non-motor and pre-motor signs and symptoms.

Resumo Passados mais de 200 anos desde a sua descrição inicial, o diagnóstico clínico da doença de Parkinson (DP) continua a ser um processo muitas vezes desafiante, com amplas implicações que são fundamentais para o manejo clínico. Apesar dos grandes desenvolvimentos na compreensão da sua patogénese, marcadores patológicos, características não motoras e potenciais pistas paraclínicas, os critérios diagnósticos mais aceitos permanecem solidamente baseados numa combinação de sinais clínicos motores. Aqui, revisamos esse processo, discutindo sua história, critérios clínicos, diagnósticos diferenciais, testes diagnósticos complementares e o papel dos sinais e sintomas não motores e pré-motores.

Effects of three physical exercise modalities on respiratory function of older adults with Parkinson's disease: A randomized clinical trial.

INTRODUCTION: Deficits in respiratory function of patients with Parkinson's disease contribute to aspiration pneumonia, one of the main causes of mortality in this population. The aim of this study was to evaluate the effects of functional training, bicycle exercise, and exergaming on respiratory function of elderly with Parkinson's disease. METHODS: A randomized clinical trial with single blinding was conducted in a public reference outpatient clinic for the elderly. The participants were randomly assigned to three groups. Group 1 was submitted to functional training (n = 18); group 2 performed bicycle exercise (n = 20), and group 3 trained with Kinect Adventures exergames (n = 20). The sessions performed lasted 8 weeks with a frequency of three 50-min sessions per week. The primary outcome was the forced expiratory volume in the first second; and the secondary outcomes were forced vital capacity, peak expiratory flow, and maximum inspiratory and expiratory pressures. RESULTS: The interventions performed did not improve the forced expiratory volume in the first second, forced vital capacity, and peak expiratory flow. However, group 2 improved (p = 0.03) maximum expiratory pressure (from 65.5cmH2O to 73.1cmH2O) (effect size 0.47), and group 3 increased (p = 0.03) maximum inspiratory pressure (from -61.3cmH2O to -71.6cmH2O) (effect size 0.53). CONCLUSIONS: No effect was found on lung volume, forced respiratory flow and capacity of the participants with Parkinson's disease submitted to three different modalities of motor training. However, bicycle exercise and exergaming have improved expiratory and inspiratory muscle strength, respectively. NCT02622737.

[Parkinson-dementia and amyotrophic lateral sclerosis association (complex of Guam). Diagnostic challenge, Mexican patient]. / Asociación Parkinson-demencia y esclerosis lateral amiotrófica (complejo Guam). Reto diagnóstico, paciente mexicano.

Background: The Amyotrophic Lateral Sclerosis-Parkinsonism-Dementia Complex (ALS-PDC) was first described in the islands of Guam. This pathology presented its peak incidence in the 1950s. Due to the rarity of the association, we report a clinical case with this complex. The objective was to describe the nosological and pathogenic implications of these neurodegenerative disorder, since they are not frequent to find in our population. Clinical case: We present a case of Latinoamerican origin who initially manifested systemic symptoms of more than 6 years of evolution, with subsequent cognitive alterations. Later, patient began with gait disturbances and motor symptoms suggestive of parkinsonism with atypical data and data of motor neurone disease (MND). More studies were carried out and confirmed findings compatible with upper and lower motor neuron involvement. A mutation in the POLG gene was observed, related to mitochondrial depletion syndrome. Conclusion: Despite the knowledge of this association, it is an entity whose clinical diagnosis could be very difficult to achieve. In addition, molecular mechanisms have not been fully identified, the most common genes related to Parkinsonism and ALS have been excluded, and even attempts to locate the locus were made, without achieving accurate results. Unfortunately, being a neurodegenerative disease, the prognosis is fatal, with no disease-modifying treatment.

Introducción: el complejo parkinsonismo-demencia-esclerosis lateral amiotrófica fue descrito por primera vez en las islas de Guam. Esta patología presentó su pico de incidencia en los años 50. Debido a la rareza de la asociación, informamos sobre un caso clínico que la presenta. El objetivo fue describir las implicaciones nosológicas y patogénicas de este trastorno neurodegenerativo, ya que no es frecuente encontrar esta asociación en nuestra población. Caso clínico: presentamos un caso de origen latinoamericano que inicialmente se manifestó con síntomas sistémicos de más de 6 años de evolución, con posteriores alteraciones cognitivas. Después presentó alteraciones de la marcha y síntomas motores sugestivos de parkinsonismo con datos atípicos y datos de enfermedad de motoneurona. Se hicieron estudios de extensión que confirmaron hallazgos compatibles con afectación en motoneurona superior e inferior. Observamos mutación en gen POLG, relacionada con síndrome de depleción mitocondrial. Conclusión: a pesar del conocimiento de esta asociación, es una entidad cuyo diagnóstico clínico puede ser muy difícil de obtener. Además, no se han identificado del todo los mecanismos moleculares, se han excluido los genes más comunes relacionados con parkinsonismos y esclerosis lateral amiotrófica e incluso se intentó localizar el locus, sin lograr resultados certeros. Desafortunadamente al ser una enfermedad neurodegenerativa el pronóstico es fatal, sin que haya tratamiento modificador de la enfermedad.

Nigrostriatal dysfunction in RFC1-related disorder/CANVAS.

INTRODUCTION: Parkinsonism is now recognized as an additional feature in RFC1/CANVAS syndrome; however, no systematic evaluation of nigrostriatal dopaminergic function has been published so far. METHODS: This is an observational, single-center study, which analyzed 13 patients with molecular confirmation of RFC1/CANVAS. Disease severity was assessed with the SARA scale. Each subject was carefully evaluated for the presence of parkinsonian features. Dopamine transporter (DAT) imaging was acquired and reconstructed in the transverse, coronal and sagittal planes 4 h after venous injection of 99mTc-TRODAT-1. An experienced nuclear physician performed the visual analysis of all images. RESULTS: Patients had a mean age of 62.3 ± 8.8 years, and there were 9 women. The mean SARA score was 15.5 ± 5.8. Nine patients had abnormal DAT imaging results. The putamen was more frequently affected than the caudate nucleus on both sides. Considering all regions, uptake of 99mTc-TRODAT-1 did not correlate with disease duration or SARA scores. Parkinsonism was noticed in 3/13 patients, all of which had abnormal DAT scans. Interestingly, six subjects had reduced DAT imaging uptake, but no clinical signs of parkinsonism. CONCLUSION: Nigrostriatal dysfunction is frequent in RFC1/CANVAS even in the absence of clinical parkinsonism and may occur early in the disease course.

Clinical and functional correlates of parkinsonism in a population-based sample of individuals aged 75 + : the Pietà study.

BACKGROUND: Parkinsonism is strongly associated with ageing, and many studies have suggested that parkinsonian signs may affect up to half of older adults and is associated with a wide range of adverse health outcomes. We compared clinical and functional characteristics of oldest-old community-dwelling individuals with parkinsonism (parkinsonian group [PG]) to individuals without parkinsonism (non-parkinsonian group [NPG]. METHODS: The Pietà study is a population-based study conducted in Caeté, southeast Brazil, involving 607 individuals aged 75 + years submitted to an extensive clinical evaluation. A subset of 65 PG individuals (61.5% women, median age of 82 years) was compared to 542 NPG individuals (64.8% women, median age of 80 years). RESULTS: PG individuals had significantly more functional impairment, clinical comorbidities (including number of falls, loss of bladder control and dysphagia) and major depression. Multivariate analysis revealed that older age, higher UPDRSm scores, lower category fluency test (animals/minute) and delayed recall memory scores were associated with PG. This group was also more cognitively impaired, with lower performance than NPG individuals in the Mini-Mental State Examination, category fluency test (animals/minute), clock drawing and in delayed recall (p < 0.001 for all tests). UPDRSm scores were the most contributing factor to cognition that independently explained variability in functionality of the entire sample. CONCLUSION: Individuals aged 75 + years with parkinsonism were significantly more clinically and functionally impaired in this population-based sample. Cognitive dysfunction explained most of the loss of functionality in these patients. UPDRS-m scores contributed independently to explain variability in functionality in the whole sample.

Electrophysiological Characterization of Cerebellar Responses during Exploration and Grooming Behaviors in a Rat Model of Parkinsonism.

Parkinson's disease is currently a global public health challenge due to the rapid growth of aging populations. To understand its pathophysiology is necessary to study the functional correlation between the basal ganglia (BG) and the cerebellum, which are involved in motor control. Herein, we explored multiunit electrical activity (MUA) in the cerebellum of rats with induced Parkinsonism as a result of lesions following bilateral placement of electrodes and passing of current in the ventrolateral striatum (VLS). In one control group, the electrodes descended without electrical current, and another group was left intact in VLS. MUA was recorded in Sim B and Crus II lobes, and in the dentate nucleus (DN) during the execution of exploration behaviors (horizontal and vertical) and grooming. The lesioned and sham groups showed a decrease in MUA amplitude in the Crus II lobe compared to the intact group in all recorded behaviors. However, Sim B and DN did not express differences. Both electrical and physical insults to the VLS induced Parkinsonism, which results in less MUA in Crus II during the execution of motor behaviors. Thus, this type of Parkinsonism is associated with a decrease in the amplitude of Crus II.

Clinical correlates of fear of falling in progressive supranuclear palsy and multiple system atrophy.

BACKGROUND AND PURPOSE: Clinical correlates of fear of falling (FoF) are scarcely studied in patients with progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). This study was undertaken to evaluate the clinical correlates of FoF in PSP and MSA. METHODS: This cross-sectional study features motor, cognitive, and psychiatric assessment and longitudinal evaluation of falls and FoF at 6-month follow-up. RESULTS: Twenty-one patients with PSP-parkinsonism, 22 patients with MSA (13 parkinsonian type and nine cerebellar type), and 22 healthy controls were evaluated; 76.2% of patients with PSP and 86.4% of patients with MSA had FoF regardless of falls. Berg Balance Scale (p < 0.001), Tinetti Mobility Test (p < 0.01), Beck Anxiety Inventory (p = 0.001), and Beck Depression Inventory-II (p = 0.01) correlated with FoF in patients with PSP and MSA, whereas Timed Up and Go test (p = 0.01) and Starkstein Apathy Scale correlated only in MSA (p = 0.04). CONCLUSIONS: Mobility, balance, and gait performance as well as anxiety and depression in PSP and MSA, and apathy in MSA, were determinants of FoF. These findings underline the importance of a multidisciplinary approach to FoF in neurodegenerative atypical parkinsonism.

Relevance of Fluorodopa PET Scan in Dopamine Responsive Dystonia and Juvenile Parkinsonism: A Systematic Review.

BACKGROUND: Dopamine Responsive Dystonia (DRD) and Juvenile Parkinsonism (JP) are two diseases commonly presenting with parkinsonian symptoms in young patients. Current clinical guidelines offer a diagnostic approach based on molecular analysis. However, developing countries have limitations in terms of accessibility to these tests. We aimed to assess the utility of imaging equipment, usually more available worldwide, to help diagnose and improve patients' quality of life with these diseases. METHODS: We performed a systematic literature review in English using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) and meta-analysis of observational studies in epidemiology (MOOSE) protocols. We only used human clinical trials about dopamine responsive dystonia and juvenile parkinsonism patients in which a fluorodopa (FD) positron emission tomography (PET) scan was performed to identify its use in these diseases. RESULTS: We included six studies that fulfilled our criteria. We found a clear pattern of decreased uptake in the putamen and caudate nucleus in JP cases. At the same time, the results in DRD were comparable to normal subjects, with only a slightly decreased marker uptake in the previously mentioned regions by the FD PET scan. CONCLUSIONS: We found a distinctive pattern for each of these diseases. Identifying these findings with FD PET scans can shorten the delay in making a definitive diagnosis when genetic testing is unavailable, a common scenario in developing countries.

Pharmacotherapy for the management of the symptoms of Machado-Joseph Disease.

INTRODUCTION: Machado-Joseph disease or spinocerebellar ataxia type 3 (SCA3/MJD) is the leading cause of autosomal dominant ataxia worldwide. This is a slowly progressive, but very disabling disorder. Ataxia is the main clinical feature, but additional motor and non-motor manifestations may be found. Many of these manifestations are amenable to pharmacological treatments, which may impact the quality of life of affected subjects. AREAS COVERED: Authors review available literature on both disease-modifying and symptomatic pharmacological therapies for SCA3/MJD. Discussion is stratified into motor (ataxic and non-ataxic syndromes) and non-motor manifestations. Ongoing clinical trials and future perspectives are also discussed in the manuscript. EXPERT OPINION: Symptomatic treatment is the mainstay of clinical care and should be tailored for each patient with SCA3/MJD. Management of ataxia is still a challenging task, but relief (at least partial) of dystonia, pain/cramps, fatigue, and sleep disorders is an achievable goal for many patients. Even though there are no disease-modifying treatments so far, recent advances in understanding the biology of disease and international collaborations of clinical researchers are now paving the way for a new era where more clinical trials will be available for this devastating disorder.

Parkinsonism-Plus Syndrome Secondary to Neurosyphilis: Case Report and Literature Review.

Background/Objective: Neurosyphilis can be associated with a variety of clinical manifestations. There are only a few cases of neurosyphilis associated with parkinsonism-plus syndromes (PPSs) that have been reported in the literature. We describe a case of an elderly woman who presented with abnormal gait and progressive visual disturbance, probably secondary to neurosyphilis. Methods: Literature search was performed in Embase, Google Scholar, Medline, Scielo, and ScienceDirect using a set of terms that included parkinsonism, tremor, and syphilis. Case Report: A 64-year-old female was admitted because of vision problems, gait disturbances, and cognitive impairment. The neurological examination revealed bradykinesia, rigidity, and rest tremor. The pupils were bilaterally small and reacted in size to a near object but did not constrict when exposed to bright light. The conjugate eye movements showed a defective downward gaze. On neuropsychological examination, the mini-mental state exam showed a moderate cognitive impairment. Reduced phonemic fluency was observed. A positive serum venereal disease research laboratory (VDRL) test was noted. A cerebrospinal fluid analysis showed positive VDRL. Brain and cervical spine magnetic resonance imaging was normal. An electro-encephalogram showed diffused slow waves. Penicillin G was started. Six months after, the patient had a full recovery of her conjugate eye movements and cognitive functions. Upon further questioning, the patient reported no response with a levodopa attempt. Conclusions: To the authors' knowledge, two individuals developed progressive supra-nuclear palsy (PSP), and one presented corticobasal degeneration (CBD), probably associated with neurosyphilis. This is the second case to document the occurrence of a progressive supra-nuclear palsy because of syphilis.