Cognitive Complaints Assessment and Neuropsychiatric Disorders After Mild COVID-19 Infection.

OBJECTIVES: This study aimed to analyze cognitive impairment associated with long-term coronavirus disease 2019 (COVID-19) syndrome and its correlation with anxiety, depression, and fatigue in patients infected with severe acute respiratory syndrome coronavirus. METHODS: This was a cross-sectional study of 127 patients with COVID-19. Tests to screen for neuropsychiatric symptoms included the Fatigue Severity Scale, Mini-Mental State Exam 2 (MMSE-2), Symbol Digit Modalities Test (SDMT), and Hospital Anxiety and Depression Scale. RESULTS: In cognitive tests, SDMT was abnormal in 22%, being more sensitive than MMSE-2 to detect cognitive changes. Furthermore, although manifestations such as fatigue, depression, and anxiety were frequent in the post-COVID-19 phase, these 3 conditions, known to contribute to cognitive impairment, were slightly correlated with worse performance on the rapid screening tests. CONCLUSIONS: In patients with mild COVID-19 and cognitive complaints, SDMT helped to confirm disturbances in the attention domain and processing speed.

rs3851179 Polymorphism at 5' to the PICALM Gene is Associated with Alzheimer and Parkinson Diseases in Brazilian Population.

Alzheimer's (AD) and Parkinson's diseases (PD) share clinical and pathological features, suggesting that they could have common pathogenic mechanisms, as well as overlapping genetic modifiers. Here, we performed a case-control study in a Brazilian population to clarify whether the risk of AD and PD might be influenced by shared polymorphisms at PICALM (rs3851179), CR1 (rs6656401) and CLU (rs11136000) genes, which were previously identified as AD risk factors by genome-wide association studies. For this purpose, 174 late-onset AD patients, 166 PD patients and 176 matched controls were genotyped using TaqMan® assays. The results revealed that there were significant differences in genotype and allele frequencies for the SNP PICALM rs3851179 between AD/PD cases and controls, but none for CR1 rs6656401 and CLU rs11136000 intronic polymorphisms. After stratification by APOE ε4 status, the protective effect of the PICALM rs3851179 A allele in AD cases remains evident only in APOE ε4 (-) carriers, suggesting that the APOE ε4 risky allele weakens its protective effect in the APOE ε4 (+) subgroup. More genetic studies using large-sized and well-defined matched samples of AD and PD patients from mixed populations as well as functional correlation analysis are urgently needed to clarify the role of rs3851179 in the AD/PD risk. An understanding of the contribution of rs3851179 to the development of AD and PD could provide new targets for the development of novel therapies.

Genetic analysis of PARK2 and PINK1 genes in Brazilian patients with early-onset Parkinson's disease.

Parkinson's disease is the second most frequent neurodegenerative disorder in the world, affecting 1-2% of individuals over the age of 65. The etiology of Parkinson's disease is complex, with the involvement of gene-environment interactions. Although it is considered a disease of late manifestation, early-onset forms of parkinsonism contribute to 5-10% of all cases. In the present study, we screened mutations in coding regions of PARK2 and PINK1 genes in 136 unrelated Brazilian patients with early-onset Parkinson's disease through automatic sequencing. We identified six missense variants in PARK2 gene: one known pathogenic mutation, two variants of uncertain role, and three nonpathogenic changes. No pathogenic mutation was identified in PINK1 gene, only benign polymorphisms. All putative pathogenic variants found in this study were in heterozygous state. Our data show that PARK2 point mutations are more common in Brazilian early-onset Parkinson's disease patients (2.9%) than PINK1 missense variants (0%), corroborating other studies worldwide.

Dysphagia and sialorrhea: the relationship to Parkinson's disease.

CONTEXT: Dysphagia and sialorrhea in patients with Parkinson's disease are both automatically accepted as dependent on this neurological disease. OBJECTIVE: The aim were to establish if these two complaints are a consequence or associated manifestations of Parkinson's disease. METHOD: Two Parkinson's diseases groups from the same outpatients' population were studied. Patients in the first group, with dysphagia, were studied by videofluoroscopy. The second, with sialorrhea, were studied by the scintigraphic method, RESULTS: Videofluoroscopic examination of the oral, pharyngeal and esophageal phases of swallowing showed that 94% of Parkinson's diseases patients present, structural causes, not related to Parkinson's diseases, able to produce or intensify the observed disphagia. The scintigraphic examination of Parkinson's diseases patients with sialorrhea showed that there is no increase of serous saliva production. Nevertheless, showed a significantly higher velocity of saliva excretion in the Parkinson's diseases patients. CONCLUSIONS: Dysphagia can be due to the muscular rigidity often present in the Parkinson's diseases patient, or more usually by non Parkinson's disease associated causes. In Parkinson's diseases patients, sialorrhea is produced by saliva retention. Nevertheless, sialorrhea can produce discomfort in swallowing, although without a formal complaint of dysphagia. In this case, subclinical dysphagia must be considered. Sialorrhea is indicative of dysphagia or at least of subclinical dysphagia. As final conclusion, Parkinson's diseases can be an isolated cause of dysphagia and/or sialorrhea, but frequently, a factor unrelated to Parkinson's diseases is the main cause of or at least aggravates the dysphagia.

DYSPHAGIA AND SIALORRHEA: the relationship to Parkinson's disease

Context Dysphagia and sialorrhea in patients with Parkinson's disease are both automatically accepted as dependent on this neurological disease. Objective The aim were to establish if these two complaints are a consequence or associated manifestations of Parkinson's disease. Method Two Parkinson's diseases groups from the same outpatients' population were studied. Patients in the first group, with dysphagia, were studied by videofluoroscopy. The second, with sialorrhea, were studied by the scintigraphic method, Results Videofluoroscopic examination of the oral, pharyngeal and esophageal phases of swallowing showed that 94% of Parkinson's diseases patients present, structural causes, not related to Parkinson's diseases, able to produce or intensify the observed disphagia. The scintigraphic examination of Parkinson's diseases patients with sialorrhea showed that there is no increase of serous saliva production. Nevertheless, showed a significantly higher velocity of saliva excretion in the Parkinson's diseases patients. Conclusions Dysphagia can be due to the muscular rigidity often present in the Parkinson's diseases patient, or more usually by non Parkinson's disease associated causes. In Parkinson's diseases patients, sialorrhea is produced by saliva retention. Nevertheless, sialorrhea can produce discomfort in swallowing, although without a formal complaint of dysphagia. In this case, subclinical dysphagia must be considered. Sialorrhea is indicative of dysphagia or at least of subclinical dysphagia. As final conclusion, Parkinson's diseases can be an isolated cause of dysphagia and/or sialorrhea, but frequently, a factor unrelated to Parkinson's diseases is the main cause of or at least aggravates the dysphagia. .

Contexto Disfagia e sialorreia em pacientes com doença de Parkinson são automaticamente entendidos como decorrentes do comprometimento neurológico produzido pela doença de Parkinson. Objetivo Estabelecer se estas duas queixas são consequências ou manifestações associadas à doença de Parkinson. Método Dois grupos de pacientes com doença de Parkinson provenientes da mesma população ambulatorial foram estudados. O primeiro grupo com queixa de disfagia foi estudado pelo método videofluoroscópico. Um segundo grupo com sialorreia foi estudado pelo método cintigráfico. Resultados O exame videofluoroscópico das fases oral, faríngea e esofágica da deglutição mostrou que 94% das disfagias nos pacientes com doença de Parkinson eram devidas a causas estruturais não relacionadas com a doença de Parkinson e capazes de produzir ou intensificar a disfagia observada. Os exames cintigráficos dos pacientes com doença de Parkinson e sialorreia mostraram que não ocorre aumento da produção de saliva. No entanto mostrou significante aumento na velocidade de excreção da saliva nesses pacientes. Conclusões A disfagia pode ser devido à rigidez muscular frequentemente presente nos pacientes com doença de Parkinson ou mais frequentemente por causas associadas que independem desta. Nos pacientes com doença de Parkinson a sialorreia é produzida pela retenção oral da saliva. Contudo é possível observar queixa de sialorreia sem formal queixa associada de disfagia. Nesses casos, disfagia sub-clínica deve ser considerada. Sialorreia é um indicativo de disfagia ou pelo menos de disfagia sub-clínica. Como conclusão final, a doença de Parkinson pode ser ...

Dysphagia and sialorrhea

ContextDysphagia and sialorrhea in patients with Parkinson's disease are both automatically accepted as dependent on this neurological disease.ObjectiveThe aim were to establish if these two complaints are a consequence or associated manifestations of Parkinson's disease.MethodTwo Parkinson's diseases groups from the same outpatients' population were studied. Patients in the first group, with dysphagia, were studied by videofluoroscopy. The second, with sialorrhea, were studied by the scintigraphic method,ResultsVideofluoroscopic examination of the oral, pharyngeal and esophageal phases of swallowing showed that 94% of Parkinson's diseases patients present, structural causes, not related to Parkinson's diseases, able to produce or intensify the observed disphagia. The scintigraphic examination of Parkinson's diseases patients with sialorrhea showed that there is no increase of serous saliva production. Nevertheless, showed a significantly higher velocity of saliva excretion in the Parkinson's diseases patients.ConclusionsDysphagia can be due to the muscular rigidity often present in the Parkinson's diseases patient, or more usually by non Parkinson's disease associated causes. In Parkinson's diseases patients, sialorrhea is produced by saliva retention. Nevertheless, sialorrhea can produce discomfort in swallowing, although without a formal complaint of dysphagia. In this case, subclinical dysphagia must be considered. Sialorrhea is indicative of dysphagia or at least of subclinical dysphagia. As final conclusion, Parkinson's diseases can be an isolated cause of dysphagia and/or sialorrhea, but frequently, a factor unrelated to Parkinson's diseases is the main cause of or at least aggravates the dysphagia.

ContextoDisfagia e sialorreia em pacientes com doença de Parkinson são automaticamente entendidos como decorrentes do comprometimento neurológico produzido pela doença de Parkinson.ObjetivoEstabelecer se estas duas queixas são consequências ou manifestações associadas à doença de Parkinson.MétodoDois grupos de pacientes com doença de Parkinson provenientes da mesma população ambulatorial foram estudados. O primeiro grupo com queixa de disfagia foi estudado pelo método videofluoroscópico. Um segundo grupo com sialorreia foi estudado pelo método cintigráfico.ResultadosO exame videofluoroscópico das fases oral, faríngea e esofágica da deglutição mostrou que 94% das disfagias nos pacientes com doença de Parkinson eram devidas a causas estruturais não relacionadas com a doença de Parkinson e capazes de produzir ou intensificar a disfagia observada. Os exames cintigráficos dos pacientes com doença de Parkinson e sialorreia mostraram que não ocorre aumento da produção de saliva. No entanto mostrou significante aumento na velocidade de excreção da saliva nesses pacientes.ConclusõesA disfagia pode ser devido à rigidez muscular frequentemente presente nos pacientes com doença de Parkinson ou mais frequentemente por causas associadas que independem desta. Nos pacientes com doença de Parkinson a sialorreia é produzida pela retenção oral da saliva. Contudo é possível observar queixa de sialorreia sem formal queixa associada de disfagia. Nesses casos, disfagia sub-clínica deve ser considerada. Sialorreia é um indicativo de disfagia ou pelo menos de disfagia sub-clínica. Como conclusão final, a doença de Parkinson pode ser causa isolada de disfagia e ou sialorreia, mas frequentemente um fator não relacionado com a doença de Parkinson pode cursar como a principal causa ou pelo menos como causa agravante da disfagia.

Depression in Parkinson's disease: diagnosis and treatment.

The prevalence of non-motor symptoms in Parkinson's disease (PD) is high. Depression varies from 20 to 50% of the PD patients, and is associated with increasing disability. The key characteristics of depression are anhedonia and low mood. The recommended scales for screening purposes are: HAM-D, BDI, HADS, MADRS and GDS. As for measurement of severity: HAM-D, MADRS, BDI and SDS. In cases with mild depression, non-pharmacological intervention is the treatment of choice. In moderate depression, antidepressants are required. The choice of an antidepressant should be based mainly on the comorbidities and unique features of the patient. Evidence for antidepressant effectiveness is seen mostly with amitriptyline and nortriptyline, but one should be cautious in elderly patients. Other antidepressants that can be prescribed are: citalopram, escitalopram, sertraline, bupropion, trazodone, venlafaxine, mirtazapine and duloxetin. The dopaminergic agonist pramipexole is a treatment option.

Exon dosage variations in Brazilian patients with Parkinson's disease: analysis of SNCA, PARKIN, PINK1 and DJ-1 genes.

Parkinson's disease is one of the most common neurodegenerative disorders associated with aging, reaching ∼ 2% of individuals over 65 years. Knowledge achieved in the last decade about the genetic basis of Parkinson's disease clearly shows that genetic factors play an important role in the etiology of this disorder. Exon dosage variations account for a high proportion of Parkinson's disease mutations, mainly for PARKIN gene. In the present study, we screened genomic rearrangements in SNCA, PARKIN, PINK1 and DJ-1 genes in 102 Brazilian Parkinson's disease patients with early onset (age of onset ⩽ 50 years), using the multiplex ligation-dependent probe amplification method. Family history was reported by 24 patients, while 78 were sporadic cases. Screening of exon dosage revealed PARKIN and PINK1 copy number variations, but no dosage alteration was found in SNCA and DJ-1 genes. Most of the carriers harbor heterozygous deletions or duplications in the PARKIN gene and only one patient was found to have a deletion in PINK1 exon 1. Data about dosage changes are scarce in the Brazilian population, which stresses the importance of including exon dosage analysis in Parkinson's disease genetic studies.

Disautonomia na doença de Parkinson. Revisão da literatura / Dysautonomy in Parkinson's disease. Review of the literature

Desde o trabalho original, são conhecidos alguns distúrbios autonômicos associados à doença de Parkinson, tais como, sialorréia, disfagia e constipação intestinal. Nesta revisão, descrevemos as principais alterações gastrointestinais, cardiovasculares, urinárias, sexuais, termorregulatórias e cutâneas. Apesar da alta prevalência (14 a 80%), continuam inadequadamente diagnosticadas.

Since the original manuscript, it has become known that some autonomic disorders are associated with Parkinson´s disease, such as sialorrhea, dysphagia and constipation. In this review we describe the main gastrointestinal, cardiovascular, urinary, sexual, thermoregulatory and cutaneous dysfunctions. Despite the high prevalence of these disorders (14 to 80%), they remain underdiagnosed.

Psychogenic dystonia induced by peripheral trauma: case report

The origin of dystonia is a point of discussion since its first description. A cause-and-effect relationship between brain injury and subsequent movement disorder is well established, but the existence of such a relationship following peripheral injury has not been universally accepted. This paper has the objective to report a patient with fixed dystonic posture of the hand after peripheral trauma.

A origem da distonia continua sendo controversa como nas suas primeiras descrições. A relação de causa e efeito entre traumatismo craniano e distúrbios do movimento está bem estabelecida, no entanto, a existência de tal relação após trauma periférico não é amplamente aceita. Este trabalho tem por objetivo relatar um paciente com postura distônica fixa da mão após trauma periférico.

Mutational analysis of GIGYF2, ATP13A2 and GBA genes in Brazilian patients with early-onset Parkinson's disease.

In the last decade, several genes have been linked to Parkinson's disease (PD), including GIGYF2, ATP13A2 and GBA. To explore whether mutations in these genes contribute to development of PD in the Brazilian population, we screened 110 patients with early-onset PD. No clearly pathogenic mutations were identified in ATP13A2 and GIGYF2. In contrast, we identified a significantly higher frequency of known pathogenic mutations in GBA gene among the PD cases (6/110=5.4%) when compared to the control group (0/155) (P=0.0047). Our results strongly support an association between GBA gene mutations and an increased risk of PD. Mutations in GIGYF2 and ATP13A2 do not seem to represent a risk factor to the development of PD in the Brazilian population. Considering the scarcity of studies on GIGYF2, ATP13A2 and GBA mutation frequency in Latin American countries, we present significant data about the contribution of these genes to PD susceptibility.

Parkinsonism and AIDS: a clinical comparative study before and after HAART.

In 2002, after analyzing 28 HIV-positive patients with movement disorders we emphasized the decreasing not only of Parkinsonism but also of other involuntary movements in HIV patients in the last few years. The objective of this study is to compare the clinical results between HIV-positive patients with Parkinsonism before and after HAART. In 14 years (1986-1999) 2,460 HIV-positive patients were seen in our Hospital 14 (0.6%) of which presented with Parkinsonism. Eight years after (2000-2007) 970 HIV positive patients were seen and only two (0.2%) had Parkinsonism. We conclude that after the introduction of HAART there was an evident decrease in AIDS-related Parkinsonism.

Parkinsonism and AIDS: a clinical comparative study before and after HAART

In 2002, after analyzing 28 HIV-positive patients with movement disorders we emphasized the decreasing not only of Parkinsonism but also of other involuntary movements in HIV patients in the last few years. The objective of this study is to compare the clinical results between HIV-positive patients with Parkinsonism before and after HAART. In 14 years (1986-1999) 2,460 HIV-positive patients were seen in our Hospital 14 (0.6 percent) of which presented with Parkinsonism. Eight years after (2000-2007) 970 HIV positive patients were seen and only two (0.2 percent) had Parkinsonism. We conclude that after the introduction of HAART there was an evident decrease in AIDS-related Parkinsonism.

No ano de 2002, após analisarmos 28 pacientes HIV-positivos que apresentavam distúrbios do movimento, enfatizamos o declínio, não só do parkinsonismo, como também de outros movimentos involuntários em pacientes infectados pelo HIV nos últimos anos. O objetivo deste estudo é comparar os resultados clínicos entre pacientes HIV-positivos com parkinsonismo antes e depois da introdução do esquema HAART. Em 14 anos (1986-1999), 2.460 pacientes HIV-positivos foram avaliados em nosso Hospital dos quais 14 (0,6 por cento) apresentaram parkinsonismo. Nos oito anos seguintes (2000-2007), 970 pacientes HIV-positivos foram avaliados e somente dois (0,2 por cento) tinham parkinsonismo. Concluímos que após a introdução do esquema HAART houve evidente declínio do parkinsonismo secundário à AIDS.

Correlações anatomoclínicas na doença de Parkinson / Anatomoclinical Correlation in Parkinson´s Disease

Braak et al., em 2003, sugeriram que o processo patológico da doença de Parkinson se iniciava nos núcleos motor dorsal do vago e olfativo anterior, com progressão caudo-rostral, em seis estágios. O presente trabalho tem por finalidade correlacionar esses estágios neuropatológicos com as suas respectivas manifestações clínicas. No estágio 1, as alterações bulbares e no núcleo olfativo anterior levam a constipação intestinal, a distúrbios do sono e a hiposmia. No estágio 2, o comprometimento pontino pode induzir a depressão, a ansiedade, a distúrbios do sono e a dor de origem central. No estágio 3, a degeneração no mesencéfalo determina o aparecimento dos sintomas motores clássicos, dos distúrbios cognitivos leves e do ciclo sono-vigília. No estágio 4, as lesões saem do tronco cerebral e atingem, principalmente, o mesocórtex temporal e a amígdala, gerando as disfunções mnemônicas, executivas e a apatia. No estágio 5, as alterações acometem o neocórtex com destaque para as áreas pré-frontais e de associação sensitivas, acentuando as disfunções cognitivas. No estágio 6, a etapa mais avançada, ocorre o comprometimento difuso das áreas corticais primárias e, por conseqüência, o agravamento das dificuldades motoras e do quadro demencial. Os Autores consideram que essas observações possam contribuir, no futuro, para possíveis benefícios terapêuticos.

Braak et al., in 2003, suggested that the pathological process of Parkinson?s disease begins at the dorsal motor nucleus of the vagus and the anterior olfactory nucleus, in a six-stage caudorostral progression. The objective of our study is to correlate these neuropathological stages with their clinical manifestations. Stage 1-related pathology started at the medulla oblongata and the anterior olfactory nucleus, leading to intestinal constipation, sleep disorders and hyposmia. At stage 2 the lesions on the pons produce symptoms of depression, anxiety, sleep disorders and central pain. In the third stage the degeneration reaches the midbrain and the classical motor symptoms appear as well as mild cognitive and sleep disorders. Stage 4 - related lesions advance upwards and exit the brain stem to the temporal mesocortex and amygdala resulting in mnemonic and executive dysfunctions and apathy. At stage 5 the lesions progress to the neocortex, mainly the prefrontal and sensory association areas, worsening the cognitive dysfunctions. At stage 6, the most advanced phase, there is the spreading of the process into the primary cortical areas, further worsening the motor symptoms and dementia. The Authors speculate that these observations could contribute to the improvement of therapeutic strategies in the future.

A study of LRRK2 mutations and Parkinson's disease in Brazil.

Mutations in the Leucine-rich repeat kinase 2 (LRRK2) gene are known as a common cause of Parkinson's disease (PD) among patients from different geographic origins. In this study, we evaluated the prevalence of LRRK2 mutations in exons 31 and 41 in a cohort of 154 consecutive, unrelated Brazilian patients with familial or sporadic PD, including early and late onset patients. The LRRK2 p.G2019S mutation was present in heterozygous state in three index cases (approximately 2%), and in three additional relatives. No carriers of this mutation were found among 250 control chromosomes. Clinically, all mutation-positive patients presented a typical PD phenotype and a good response to levodopa. Mutation segregation analysis in a large sibling showed incomplete penetrance of the p.G2019S. Our findings suggest that the LRRK2 p.G2019S mutation has a substantial contribution to PD susceptibility among Brazilian population and add new clues to current research of this disease.

Scintigraphic analysis of the parotid glands in patients with sialorrhea and Parkinson's disease.

Since sialorrhea was initially described, it has been associated with Parkinson's disease (PD) but until now little is known about its pathophysiology. The authors studied parotid gland activity using scintigraphic analysis on 14 PD patients with sialorrhea and in eight healthy persons with matching ages. There was no difference between uptake and intra-glandular distribution by the parotid gland in the two groups but the parotid excretion speed in the PD patients was greater than that observed in healthy individuals. Our results reject the hypothesis of PD productive sialorrhea and point to retention sialorrhea due to the increase of saliva excretion velocity.