Movement disorders in hereditary spastic paraplegias / Distúrbios de movimento em paraplegia espástica hereditária

Abstract Background Hereditary or familial spastic paraplegias (SPG) comprise a group of genetically and phenotypically heterogeneous diseases characterized by progressive degeneration of the corticospinal tracts. The complicated forms evolve with other various neurological signs and symptoms, including movement disorders and ataxia. Objective To summarize the clinical descriptions of SPG that manifest with movement disorders or ataxias to assist the clinician in the task of diagnosing these diseases. Methods We conducted a narrative review of the literature, including case reports, case series, review articles and observational studies published in English until December 2022. Results Juvenile or early-onset parkinsonism with variable levodopa-responsiveness have been reported, mainly in SPG7 and SPG11. Dystonia can be observed in patients with SPG7, SPG11, SPG22, SPG26, SPG35, SPG48, SPG49, SPG58, SPG64 and SPG76. Tremor is not a frequent finding in patients with SPG, but it is described in different types of SPG, including SPG7, SPG9, SPG11, SPG15, and SPG76. Myoclonus is rarely described in SPG, affecting patients with SPG4, SPG7, SPG35, SPG48, and SPOAN (spastic paraplegia, optic atrophy, and neuropathy). SPG4, SPG6, SPG10, SPG27, SPG30 and SPG31 may rarely present with ataxia with cerebellar atrophy. And autosomal recessive SPG such as SPG7 and SPG11 can also present with ataxia. Conclusion Patients with SPG may present with different forms of movement disorders such as parkinsonism, dystonia, tremor, myoclonus and ataxia. The specific movement disorder in the clinical manifestation of a patient with SPG may be a clinical clue for the diagnosis.

Resumo Antecedentes As paraplegias espásticas hereditárias ou familiares (SPG) compreendem um grupo de doenças geneticamente e fenotipicamente heterogêneas caracterizadas por degeneração progressiva dos tratos corticospinais. As formas complicadas evoluem com vários outros sinais e sintomas neurológicos, incluindo distúrbios do movimento e ataxia. Objetivo Resumir as descrições clínicas de SPG que se manifestam com distúrbios do movimento ou ataxias para auxiliar o clínico na tarefa de diagnosticar essas doenças. Métodos Realizamos uma revisão da literatura, incluindo relatos de casos, séries de casos, artigos de revisão e estudos observacionais publicados em inglês até dezembro de 2022. Resultados O parkinsonismo juvenil ou de início precoce com resposta variável à levodopa foi relatado principalmente em SPG7 e SPG11. A distonia pode ser observada em pacientes com SPG7, SPG11, SPG22, SPG26, SPG35, SPG48, SPG49, SPG58, SPG64 e SPG76. O tremor não é um achado frequente em pacientes com SPG, mas é descrito em diferentes tipos de SPG, incluindo SPG7, SPG9, SPG11, SPG15 e SPG76. A mioclonia é raramente descrita em SPG, afetando pacientes com SPG4, SPG7, SPG35, SPG48 e SPOAN (paraplegia espástica, atrofia óptica e neuropatia). SPG4, SPG6, SPG10, SPG27, SPG30 e SPG31 podem raramente apresentar ataxia com atrofia cerebelar. E SPG autossômico recessivo, como SPG7 e SPG11, também pode apresentar ataxia. Conclusão Indivíduos com SPG podem apresentar diferentes formas de distúrbios do movimento, como parkinsonismo, distonia, tremor, mioclonia e ataxia. O distúrbio específico do movimento na manifestação clínica de um paciente com SPG pode ser uma pista clínica para o diagnóstico.

Group physiotherapy and quality of life in parkinsonism: quasi-experimental study

According to systematic reviews, a short-term treatment of aquatic physiotherapy, mind-body therapies and exergame improve quality of life of people with parkinsonism. But few studies examined the group physiotherapy effects on quality of life of people with parkinsonism. Objective: We aimed to investigate the short-term effects of group physiotherapy protocols on the quality of life of people with Parkinson's disease or secondary parkinsonism. Methods: This is a quasi-experimental study, a controlled, non-randomized, unmasked trial, with consecutive arms for one group and parallel to another, with 15 participants with parkinsonism. They were organized in 3 groups: OG-E1wI (n = 9), observed group treated with group physiotherapy once a week; EG-C (n = 6), in the control phase without treatment, concomitant with OG-E1wI; EG-2wI (n = 6), the same subjects as EG-C, they were treated with group physiotherapy twice a week, in a posterior consecutive phase. The PDQ-39 scale was used to assess Quality of Life. Results: The mean differences between OG-E1wI and EG-C and between EG-2wI and EG-C in the various domains of PDQ-39 were not statistically significant. Conclusion: A group physiotherapy protocols performed once or twice a week may not be enough to improve quality of life for people with parkinsonism. The literature suggests that group physiotherapy protocols performed three to five times a week improve quality of life in a short period

Contexto: Revisões sistemáticas sugerem que fisioterapia aquática, terapias corporais complementares e exergame aumentam a qualidade de vida da pessoa com parkinsonismo em tratamento de curto prazo. Porém, os efeitos da fisioterapia em grupo na qualidade de vida da pessoa com parkinsonismo são pouco estudados. Objetivo: Investigar os efeitos em curto prazo de protocolos de fisioterapia grupal sobre a Qualidade de Vida de pessoas com doença de Parkinson e parkinsonismo secundário. Métodos: Estudo quasi-experimental, ensaio controlado não randomizado, sem mascaramento, com braços consecutivos para um grupo e paralelo para outro, com 15 participantes com parkinsonismo. Os participantes foram organizados em 3 grupos: OG-E1wI (n= 9), intervenção de fisioterapia em grupo uma vez por semana; EG-C (n= 6), em fase controle sem tratamento, concomitante ao OG-E1wI; EG-2wI (n=6), os mesmos sujeitos do EG-C, em fase consecutiva com intervenção de fisioterapia em grupo, duas vezes por semana. A escala PDQ-39 foi utilizada para avaliar a Qualidade de Vida. Resultados: As diferenças médias entre OG-E1wI e EG-C e entre EG-2wI e EG-C nos vários domínios da PDQ-39 não são estatisticamente significativas. Conclusão: Protocolos de fisioterapia em grupo com frequência de uma ou duas vezes por semana podem não ser suficiente para promover ganhos na qualidade de vida de pessoas com parkinsonismo. A literatura sugere que protocolos de fisioterapia em grupo feitos três a cinco vezes por semana obtêm ganho de qualidade de vida em um período de curto prazo

Multiple cerebral infarction complicated with vascular Parkinsonism on cognitive function in patients / 公共卫生与预防医学

Objective To analyze the influence of patients with multiple cerebral infarction complicated with vascular Parkinsonism (VaP) on cognitive function, and to provide a theoretical basis for the diagnosis and treatment of patients with multiple cerebral infarction complicated with VaP. Methods A toatl of 206 patients with multiple cerebral infarction admitted to Ningde municipal hospital of ningde normal university from January 2020 to January 2022 were selected and divided into VaP group (n=58) and control group (n=148) according to whether they were complicated with VaP. Montreal Cognitive Assessment Scale (MoCA) was used to evaluate the cognitive function of patients. The scale included 8 cognitive domains including attention and concentration, executive function, memory, language, visual structure skills, abstract thinking, calculation and orientation. Pearson was used to analyze the correlation between VaP and MoCA score in patients with multiple cerebral infarction. Age, sex, years of education, white matter disease, diabetes mellitus, coronary heart disease and other vascular risk factors were compared between the two groups. The independent risk factors for VaP in multiple cerebral infarction were analyzed by multiple linear regression. Results MoCA score in VaP group was significantly lower than that in control group (P<0.05). In terms of each item, scores of attention and concentration, memory, language and computation in VaP group were significantly lower than those in control group (P<0.05). Pearson correlation analysis showed that attention and concentration, memory, language and computational scores were correlated with VaP in patients with multiple cerebral infarction (r=-0.475, -0.314 , -0.302 , -0.389, P<0.05). There were statistically significant differences between the two groups in white matter lesions, lesion sites in left hemisphere and frontal lobe, diabetes mellitus and carotid artery plaque (P<0.05).White matter lesions (OR=2.571), diabetes mellitus (OR=2.369) and lesion location in the left hemisphere (OR=2.958) were independent risk factors for VaP in patients with multiple cerebral infarction (P<0.05). Conclusion The risk of VaP in multiple cerebral infarction is high, which is related to the cognitive function of patients. Early intervention such as brain function training should be given to patients with white matter lesions, diabetes and lesions in the left hemisphere. , can significantly improve patients' cognitive function and reduce the occurrence of VaP.

Interpretation of presynaptic dopaminergic PET imaging results / 中华核医学与分子影像杂志

Presynaptic dopaminergic PET imaging is a useful method for the diagnosis of parkinsonism. Based on the expert consensus on operation and clinical application of dopamine transporter brain PET imaging technology published in 2020, this paper further recommends the relevant elements of result interpretation of presynaptic dopaminergic PET imaging.

China Hospital Pharmacovigilance System-based study of trimetazidine-associated Parkinson's syndrome / 中国基层医药

Objective:To evaluate the active monitoring methods and population characteristics of trimetazidine-associated Parkinson's syndrome.Methods:The clinical data of patients with trimetazidine-associated Parkinson's syndrome who received treatment in Liaocheng People's Hospital from January 2019 to December 2020 were retrospectively analyzed using the China Hospital Pharmacovigilance System (CHPS).Results:In 4 883 patients included in the study,167 patients were alarmed by CHPS, of which 26 patients were confirmed positive by manual rechecks. The rate of positive pre-alarming by CHPS was 15.57%. The actual incidence of trimetazidine-associated Parkinson's syndrome was 0.53%. The average age of the 26 patients with Parkinson's syndrome was (75.08 ± 10.79) years. None of the 26 patients had a past history/family history of idiopathic Parkinson's disease. There were 21 patients (80.77%) aged over 65 years, 19 patients (73.08%) with a history of ischemic encephalopathy, 17 patients (65.38%) with positive symptoms in both limbs, 20 patients (76.92%) with abnormal brain CT or MRI findings, and 21 patients (80.77%) with medication doses of 60-70 mg/d. Among the 26 patients, 18 were female patients (69.23%) and 18 were patients with normal renal function (69.23%). The follow-up results showed that trimetazidine administration was not terminated in 14 patients (53.85%), symptoms were not alleviated or worsened in 8 patients (30.77%), and symptoms were alleviated or disappeared in 18 patients (69.23%).Conclusion:The use of CHPS can timely detect trimetazidine-associated Parkinson's syndrome. CHPS has significant advantages over traditional monitoring modes. Age > 65 years and a previous history of ischemic encephalopathy are risk factors for developing trimetazidine-associated Parkinson's syndrome. No history/family history of idiopathic Parkinson's disease, positive Alzheimer's disease symptoms in both limbs and abnormal brain CT and MRI findings contribute to early diagnosis and differentiation of trimetazidine- associated Parkinson's syndrome. Trimetazidine-associated Parkinson's syndrome is more common in women than in men. Trimetazidine-associated Parkinson's syndrome can also occur in a population with normal renal function or under a normal trimetazidine dose condition. Trimetazidine-associated Parkinson's syndrome is relatively rare. Patients with trimetazidine- associated Parkinson's syndrome have low awareness. Because of the difficult diagnosis and serious consequences, there is a need to strengthen research on trimetazidine-associated Parkinson's syndrome.

Feasibility of telemedicine for patients with parkinsonism in the Brazilian public health system / Viabilidade da telemedicina para pacientes com parkinsonismo no sistema público de saúde brasileiro

Abstract Background Telemedicine for patients with parkinsonism is feasible, cost-effective and satisfactory. However, the feasibility of this modality of care for this subpopulation is not known in real-life scenarios of developing countries like Brazil. Objective To evaluate the feasibility of telemedicine for patients with parkinsonism in a developing country. Methods A cross-sectional study with patients with parkinsonism treated in the Brazilian public healthcare system. We included 130 patients, who were contacted by telephone; those who could be reached underwent a structured interview for data collection. The primary outcomes were the feasibility of teleconsultations and video consultations, but we also performed a logistic regression regarding the feasibility of a video consultation and associated factors. Results Telemedicine was feasible and accepted by 69 (53.08%) patients regarding teleconsultations and by 50 (38.5%) patients regarding video consultations. Tele-consultations were feasible for 80.2%, and video consultations were feasible for 58.1% of the patients reachable through telephone calls. Having a higher family income was positively correlated with the feasibility for a video consultation while a negative association was observed regarding being married or in a stable union and having a low level of schooling. Conclusions A significant proportion of patients with parkinsonism in a developing country are unreachable, unwilling, or unable to participate in telemedicine. Among the reachable patients, feasibility is higher but still lower than what is reported in studies in developed countries. Family income, level of schooling, and marital status were associated with the feasibility of video consultations.

Resumo Antecedentes A telemedicina para pacientes com parkinsonismo é viável, econômica e satisfatória. No entanto, a viabilidade dessa modalidade de atendimento para essa subpopulação não é conhecida no cenário da vida real de países em desenvolvimento como o Brasil. Objetivo Avaliar a viabilidade da telemedicina para pacientes com parkinsonismo em um país em desenvolvimento. Métodos Estudo transversal com pacientes com parkinsonismo atendidos na rede pública de saúde brasileira. Foram incluídos 130 pacientes, que foram contatados por telefone; os que responderam foram submetidos a uma entrevista estruturada para coleta de dados. Os resultados primários foram a viabilidade para teleconsultas e videoconsultas, mas também foi realizada uma regressão logística entre a viabilidade de uma videoconsulta e fatores associados. Resultados A participação em telemedicina era possível ou consentida por 69 (53,08%) dos pacientes com relação a teleconsultas, e por 50 (38,5%) com relação a videoconsultas. As teleconsultas e videoconsultas eram viáveis para 80,2% e 58,1% dos pacientes acessíveis por telefone, respectivamente. Uma maior renda familiar foi positivamente correlacionada com a viabilidade de uma videoconsulta, enquanto uma associação negativa foi observada com relação a ser casado ou estar em união estável e ter baixo grau de escolaridade. Conclusões Uma proporção significativa de pacientes com parkinsonismo em um país em desenvolvimento é inacessível, não quer, ou não pode participar da tele-medicina. Entre os pacientes contatáveis, a viabilidade é maior, mas ainda menor do que a relatada em estudos em países desenvolvidos. Renda familiar, escolaridade e estado civil foram associados à viabilidade das videoconsultas.

Progressive supranuclear palsy and corticobasal degeneration: novel clinical concepts and advances in biomarkers / Paralisia supranuclear progressiva e degeneração corticobasal: novos conceitos clínicos e avanços em biomarcadores

ABSTRACT Background: Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are sporadic adult-onset primary tauopathies clinically classified among the atypical parkinsonian syndromes. They are intrinsically related with regard to their clinical features, pathology, biochemistry, and genetic risk factors. Objectives: This review highlights the current knowledge on PSP and CBD, focusing on evolving clinical concepts, new diagnostic criteria, and advances in biomarkers. Methods: We performed a non-systematic literature review through the PubMed database. The search was restricted to articles written in English, published from 1964 to date. Results: Clinicopathologic and in vivo biomarkers studies have broadened PSP and CBD clinical phenotypes. They are now recognized as a range of motor and behavioral syndromes associated with underlying 4R-tauopathy neuropathology. The Movement Disorders Society PSP diagnostic criteria included clinical variants apart from the classical description, increasing diagnostic sensitivity. Meanwhile, imaging biomarkers have explored the complexity of symptoms and pathological processes related to corticobasal syndrome and CBD. Conclusions: In recent years, several prospective or clinicopathologic studies have assessed clinical, radiological, and fluid biomarkers that have helped us gain a better understanding of the complexity of the 4R-tauopathies, mainly PSP and CBD.

RESUMO Antecedentes: A paralisia supranuclear progressiva (PSP) e a degeneração corticobasal (DCB) são taupatias esporádicas primárias clinicamente classificadas no grupo das síndromes parkinsonianas atípicas. Ambas estão intrinsecamente relacionadas no que concerne aos aspectos clínicos, patológicos, bioquímicos e genéticos. Objetivos: Abordar os avanços recentes no conhecimento da PSP e DCB, focando na evolução dos conceitos clínicos, critérios diagnósticos, e avanços em biomarcadores. Métodos: Trata-se de uma revisão não-sistemática através da base de dados PubMed. Foram revisados artigos escritos em língua inglesa, publicados desde 1964 até a presente data. Resultados: Estudos com biomarcadores e análises postmortem ampliaram os fenótipos conhecidos da PSP e DCB. Tais doenças englobam um espectro amplo de síndromes motoras e cognitivas, associadas a neuropatologia tau com isoforma predominante 4R. O atual critério para PSP estabeleceu novas variantes clínicas para além da descrição clássica, aumentando a sensibilidade diagnóstica. Concomitantemente, biomarcadores in vivo exploraram a complexidade dos sintomas e processos patológicos relacionados à síndrome e degeneração corticobasal. Conclusões: Recentemente, alguns estudos prospectivos e clinicopatológicos investigaram aspectos clínicos, radiológicos e de biofluidos, que ajudaram a melhor compreender a heterogeneidade e complexidade clínica das taupatias 4R, sobretudo PSP e DCB.

Magnetic resonance and dopamine transporter imaging for the diagnosis of Parkinson´s disease: a narrative review / Ressonância magnética e neuroimagem do transportador de dopamina no diagnóstico da doença de Parkinson: uma revisão narrativa

ABSTRACT Background: the diagnosis of Parkinson's disease (PD) can be challenging, especially in the early stages, albeit its updated and validated clinical criteria. Recent developments on neuroimaging in PD, altogether with its consolidated role of excluding secondary and other neurodegenerative causes of parkinsonism, provide more confidence in the diagnosis across the different stages of the disease. This review highlights current knowledge and major recent advances in magnetic resonance and dopamine transporter imaging in aiding PD diagnosis. Objective: This study aims to review current knowledge about the role of magnetic resonance imaging and neuroimaging of the dopamine transporter in diagnosing Parkinson's disease. Methods: We performed a non-systematic literature review through the PubMed database, using the keywords "Parkinson", "magnetic resonance imaging", "diffusion tensor", "diffusion-weighted", "neuromelanin", "nigrosome-1", "single-photon emission computed tomography", "dopamine transporter imaging". The search was restricted to articles written in English, published between January 2010 and February 2022. Results: The diagnosis of Parkinson's disease remains a clinical diagnosis. However, new neuroimaging biomarkers hold promise for increased diagnostic accuracy, especially in earlier stages of the disease. Conclusion: Future validation of new imaging biomarkers bring the expectation of an increased neuroimaging role in the diagnosis of PD in the following years.

RESUMO Antecedentes: O diagnóstico da doença de Parkinson (DP) pode ser desafiador, principalmente nas fases iniciais da doença, embora tenha critérios clínicos atualizados e validados. Os avanços recentes em neuroimagem na DP, além do seu papel já consolidado de excluir causas secundárias e outras causas neurodegenerativas de parkinsonismo, tem contribuído para uma maior confiabilidade no diagnóstico em diferentes estágios da doença. Nesta revisão, nós destacamos os principais avanços de ressonância magnética e imagem do transportador de dopamina em auxiliar o diagnóstico de DP. Objetivo: realizar uma revisão acerca do conhecimento atual sobre o papel da ressonância magnética e imagem do transportador de dopamina no diagnóstico de doença de Parkinson. Método: Realizamos uma revisão não sistemática da literatura através da base de dados PubMed, utilizando as palavras-chave "Parkinson", "magnetic resonance imaging", "diffusion tensor", "diffusion-weighted", "neuromelanin", "nigrosome-1", "single-photon emission computed tomography", "dopamine transporter imaging". A busca foi restrita a artigos escritos em inglês, publicados entre janeiro de 2010 e fevereiro de 2022. Resultados: O diagnóstico de doença de Parkinson continua sendo um diagnóstico clínico, contudo, novos biomarcadores de neuroimagem são promissores para o aumento da acurácia diagnóstica, especialmente em fases mais precoces da doença. Conclusão: A validação futura de novos biomarcadores de imagem traz a expectativa de um maior papel da neuroimagem no diagnóstico de doença de Parkinson nos próximos anos.

PLA2G6 gene related early onset Parkinson syndrome with cerebellar atrophy: 3 cases report / 中华神经科杂志

To investigate the clinical features of patients with PLA2G6 gene related early onset Parkinson syndrome (EOP) with cerebellar atrophy, the clinical data of 3 hospitalized EOP patients with PLA2G6 gene mutation were collected in Xuanwu Hospital, Capital Medical University, and the clinical characteristics, imaging features and genetic testing results were comparatively analyzed. Related literatures were also reviewed. Cerebellar atrophy was observed on cranial magnetic resonance imaging in all 3 patients with Parkinson syndrome except for extrapyramidal symptoms. All 3 patients had heterozygous mutations of PLA2G6 gene, and the common mutation site of c.991G>T (p. D331Y) was found in 2 patients by second-generation sequencing. This report enlarges the clinical phenotypic spectrum of the disease and helps to better understand the disease.

Application of combining 18F-FDG PET imaging and radiomics in the diagnosis of Parkinson′s disease and atypical parkinsonian syndromes / 中华核医学与分子影像杂志

Objective:To explore the potential application of combining 18F-FDG PET imaging and radiomics in the diagnosis of Parkinson′s disease (PD) and atypical parkinsonian syndromes (APS). Methods:A total of 154 subjects of two cohorts (training set and validation set) were enrolled from Huashan Hospital, Fudan University from March 2015 to August 2020 in this cross-sectional study, including 40 normal controls (NC; 23 males and 17 females, age: (60.2±10.5) years), 40 PD patients (20 males and 20 females, age: (64.7±6.3) years), 40 progressive supranuclear palsy (PSP) patients (20 males and 20 females, age: (64.1±5.9) years), and 34 multiple system atrophy (MSA) patients (19 males and 15 females, age: (65.0±9.2) years). 18F-FDG PET images and clinical scale were selected, and one-way analysis of variance was used to compare differences of clinical scale among groups. Radiomic features extraction and feature selection were carried out. Two and three classification models were constructed based on logistic regression, and the ROC curves of clinical model, radiomics model and combined model were calculated. Independent classification tests were conducted 100 times with 5-fold cross validation in two cohorts. Results:There were significant differences in the scores of unified PD Rating Scale (UPDRS) and Hoehn-Yahr rating scale (H&Y) among different groups in cohort 1 and cohort 2 respectively ( F values: 4.83-17.95, all P<0.05). A total of 2 444 imaging features were extracted from each subject, and after features selection, 15 features for classification were obtained. In the two classification experiment, the AUCs of the three models in binary classification of PD/MSA/PSP/NC group were 0.56-0.68, 0.74-0.93 and 0.72-0.93, respectively. The classification effects of the radiomics model were significantly better than those of the clinical model ( z values: 1.71-2.85, all P<0.05). In the three classification experiment, the sensitivity of the radiomics model reached 80%, 80% and 77% for PD, MSA and PSP, respectively. Conclusion:18F-FDG imaging combined with radiomics has potential in the diagnosis of PD and APS.

Glutamatergic Neurons in the Caudal Zona Incerta Regulate Parkinsonian Motor Symptoms in Mice / 神经科学通报·英文版

Parkinson's disease (PD) is the second most common and fastest-growing neurodegenerative disorder. In recent years, it has been recognized that neurotransmitters other than dopamine and neuronal systems outside the basal ganglia are also related to PD pathogenesis. However, little is known about whether and how the caudal zona incerta (ZIc) regulates parkinsonian motor symptoms. Here, we showed that specific glutamatergic but not GABAergic ZIc

Anti-neurexin-3α antibody-associated encephalitis with parkinsonism as the main manifestation: a case report / 中华神经科杂志

Anti-neurexin-3α antibody-associated encephalitis is rare in clinical practice. It often has a history of pre-infection. It is characterized by abnormal mental behavior, seizures, decreased consciousness, cognitive and sleep disorders, movement disorder, central hypoventilation and autonomic nervous dysfunction. Among them, dyskinesias are mainly involuntary movements of the mouth, face and limbs, dystonia, myoclonic seizures and other manifestations of increased movement. Parkinson′s symptoms manifested as decreased movement are rarely reported. A encephalitis patient with positive anti-neurexin-3α antibody is reported, who is a young female, mainly with parkinsonism such as slow movement, unsteady walking, difficulty in starting and turning around, and inability to hold things in both upper limbs, accompanied by abnormal mental behavior and cognitive dysfunction. After treatment with methylprednisolone and intravenous immunoglobulin, the prognosis is good.

Parkinson genetico: Reporte de un caso clínico y revisión de la literatura / Genetic Parkinson disease: a case report and literature review

RESUMEN El parkinsonismo constituye un conjunto de signos y síntomas clínicos caracterizados por bradicinesia y temblor en reposo o rigidez, cuya causa más frecuente es la enfermedad de Parkinson (EP). La gran mayoría de los casos de EP son esporádicos, sin embargo, existe una minoría en la cual la etiología se debe a una mutación heredada, ya sea autosómica dominante (AD), autosómica recesiva (AR) o herencia ligada al X. La identificación de estas causas heredables es importante para una adecuada consejería genética y tratamiento. Se presenta el caso de un paciente con EP de inicio temprano en el que se identificó una mutación AD en el gen GIGYF2 o PARK11, asociado a una breve revisión de la literatura

SUMMARY Parkinsonism constitutes a set of clinical signs and symptoms characterized by bradykinesia and tremor at rest and / or rigidity. The main etiology is Parkinson's disease (PD), but there are other causes such as atypical parkinsonism. The vast majority of PD cases are sporadic, however, there is a minority where the etiology is due to an inherited mutation, either autosomal dominant (AD), autosomal recessive (RA), or X-linked inheritance. Identifying these heritable causes is important for proper genetic counseling and treatment. We present the case of a patient with early-onset PD where an AD mutation in the GIGYF2 gene (PARK11) was identified. We subsequently present a brief review of the literature.

Correlation between 99mTc-TRODAT-1 SPECT and 18F-FDOPA PET in patients with Parkinson's disease: a pilot study / Correlação entre 99mTc-TRODAT-1 SPECT e 18F-FDOPA PET em pacientes com doença de Parkinson: um estudo piloto

Abstract Objective: To determine whether technetium-99m-labeled tropane derivative single-photon emission computed tomography (99mTc-TRODAT-1 SPECT) provides results comparable to those of the less widely available, less accessible tool fluorine-18-labeled fluorodopa positron-emission tomography (18F-FDOPA PET) in the setting of a movement disorders clinic. Materials and Methods: In this prospective pilot study, eight subjects with a clinical diagnosis of Parkinson's disease were randomly selected from among patients under treatment at a movement disorders clinic and submitted to 99mTc-TRODAT-1 SPECT and 18F-FDOPA PET. The results were read by two experienced observers, and a semiquantitative analysis was performed. Results: The visual and semiquantitative analyses were concordant for all studies, showing that radiotracer uptake in the contralateral striatum on the most affected side was lower when 99mTc-TRODAT-1 SPECT was employed. The semiquantitative analysis demonstrated a significant correlation between 18F-FDOPA PET and 99mTc-TRODAT-1 SPECT (r = 0.73; p < 0.01). Conclusion: It appears that 99mTc-TRODAT-1 SPECT is a valid option for the study of dopaminergic function in a clinical setting.

Resumo Objetivo: Determinar se a 99mTc-TRODAT-1 SPECT fornece resultados comparáveis aos da 18F-FDOPA PET, ferramenta menos acessível e menos amplamente disponível, no contexto de uma clínica de distúrbios do movimento. Materiais e Métodos: Neste estudo prospectivo, oito indivíduos com diagnóstico clínico de doença de Parkinson foram selecionados aleatoriamente entre pacientes em tratamento em uma clínica de distúrbios do movimento e submetidos a 99mTc-TRODAT-1 SPECT e 18F-FDOPA PET. Os resultados foram lidos por dois observadores experientes e uma análise semiquantitativa foi realizada. Resultados: As análises visual e semiquantitativa foram concordantes para todos os estudos, mostrando que a captação do radiotraçador no estriado contralateral do lado mais afetado foi menor quando a 99mTc-TRODAT-1 SPECT foi empregada. A análise semiquantitativa demonstrou uma correlação significativa entre 18F-FDOPA PET e 99mTc-TRODAT-1 SPECT (r = 0,73; p < 0,01). Conclusão: A 99mTc-TRODAT-1 SPECT parece ser uma opção válida para o estudo da função dopaminérgica em um ambiente clínico.

Abnormal eye movements in parkinsonism: a historical view / Movimentos oculares anormais em parkinsonismo: uma visão histórica

ABSTRACT Parkinson's disease (PD), known since ancient times as paralysis agitans, was studied and described by James Parkinson in 1817 in his work "An Essay on the Shaking Palsy". Fifty years later, Charcot and his students delved into the disease, naming it as we know it today, as well as defining the classic disease and its variants. One of these students, Arthur Dutil, addressed patients' abnormal eye movements. Nowadays, it is known that the differential diagnosis of PD is relevant for prognosis, treatment and research, and, despite the advances in the area, it remains largely clinical. The relevance of the eye movement exam has grown along with the history of PD and it has proved to be an excellent tool for the differential diagnosis of parkinsonism. Additionally, it can become a support to identify different types of genetic PD and be useful for improving early recognition of cognitive decline in patients with PD.

RESUMO A doença de Parkinson (DP), conhecida desde a antiguidade como paralysis agitans, foi estudada e descrita por James Parkinson em 1817 em seu trabalho An Essay on the Shaking Palsy. Cinquenta anos depois, Charcot e seus alunos aprofundaram os estudos na doença, nomeando-a como a conhecemos atualmente, bem como definindo a doença clássica e suas variantes. Um desses estudantes, Arthur Dutil, investigou os movimentos oculares anormais nos pacientes. Hoje, sabe-se que o diagnóstico diferencial da DP é relevante para o prognóstico, tratamento e pesquisa, e, apesar dos grandes avanços na área, ainda permanece amplamente clínico. A relevância do exame de movimentação ocular cresceu com a história da DP e este se mostrou uma excelente ferramenta para o diagnóstico diferencial do parkinsonismo. Além disso, pode se tornar um auxílio para identificar diferentes formas de DP genética e útil para melhorar o reconhecimento precoce do declínio cognitivo em pacientes com DP.

Roberto Melaragno's scientific contributions to Brazilian Neurology / As contribuições científicas de Roberto Melaragno à Neurologia Brasileira

ABSTRACT Roberto Melaragno Filho, an associate professor of neurology at the School of Medicine of Universidade de São Paulo and head of the neurology service at Hospital do Servidor Público Estadual Francisco Morato Oliveira (HSPE-FMO), had a significant scientific career. He is recognized as a reference in the 20th century Brazilian neurology in addition to having a notable international career.

RESUMO Roberto Melaragno Filho, professor livre-docente em neurologia pela Faculdade de Medicina da Universidade de São Paulo, e chefe do serviço de neurologia do Hospital do Servidor Público Estadual Francisco Morato de Oliveira (HSPE-FMO), teve uma carreira científica de grande relevo, sendo reconhecido nacionalmente como uma das referências em neurologia no século XX, além de ter tido uma notável carreira internacional.

Co-editing PINK1 and DJ-1 Genes Via Adeno-Associated Virus-Delivered CRISPR/Cas9 System in Adult Monkey Brain Elicits Classical Parkinsonian Phenotype / 神经科学通报·英文版

Whether direct manipulation of Parkinson’s disease (PD) risk genes in the adult monkey brain can elicit a Parkinsonian phenotype remains an unsolved issue. Here, we used an adeno-associated virus serotype 9 (AAV9)-delivered CRISPR/Cas9 system to directly co-edit PINK1 and DJ-1 genes in the substantia nigras (SNs) of two monkey groups: an old group and a middle-aged group. After the operation, the old group exhibited all the classic PD symptoms, including bradykinesia, tremor, and postural instability, accompanied by key pathological hallmarks of PD, such as severe nigral dopaminergic neuron loss (>64%) and evident α-synuclein pathology in the gene-edited SN. In contrast, the phenotype of their middle-aged counterparts, which also showed clear PD symptoms and pathological hallmarks, were less severe. In addition to the higher final total PD scores and more severe pathological changes, the old group were also more susceptible to gene editing by showing a faster process of PD progression. These results suggested that both genetic and aging factors played important roles in the development of PD in the monkeys. Taken together, this system can effectively develop a large number of genetically-edited PD monkeys in a short time (6–10 months), and thus provides a practical transgenic monkey model for future PD studies.

Co-editing PINK1 and DJ-1 Genes Via Adeno-Associated Virus-Delivered CRISPR/Cas9 System in Adult Monkey Brain Elicits Classical Parkinsonian Phenotype / 神经科学通报·英文版

Whether direct manipulation of Parkinson's disease (PD) risk genes in the adult monkey brain can elicit a Parkinsonian phenotype remains an unsolved issue. Here, we used an adeno-associated virus serotype 9 (AAV9)-delivered CRISPR/Cas9 system to directly co-edit PINK1 and DJ-1 genes in the substantia nigras (SNs) of two monkey groups: an old group and a middle-aged group. After the operation, the old group exhibited all the classic PD symptoms, including bradykinesia, tremor, and postural instability, accompanied by key pathological hallmarks of PD, such as severe nigral dopaminergic neuron loss (>64%) and evident α-synuclein pathology in the gene-edited SN. In contrast, the phenotype of their middle-aged counterparts, which also showed clear PD symptoms and pathological hallmarks, were less severe. In addition to the higher final total PD scores and more severe pathological changes, the old group were also more susceptible to gene editing by showing a faster process of PD progression. These results suggested that both genetic and aging factors played important roles in the development of PD in the monkeys. Taken together, this system can effectively develop a large number of genetically-edited PD monkeys in a short time (6-10 months), and thus provides a practical transgenic monkey model for future PD studies.

A case report of spinocerebellar ataxia type 2 with parkinsonism and cognitive impairment / 中华神经科杂志

The common clinical manifestations of spinocerebellar ataxia type 2 include ataxia, dysarthria, slower saccades, weakened or disappeared tendon reflexes, etc. It is relatively rare in patients with parkinsonism and cognitive impairment. Parkinsonism is rare in patients with spinocerebellar ataxia type 2, maybe because the degeneration of the substantia nigra striatum system is only manifested in the striatal presynaptic membrane, while the postsynaptic membrane receptors are relatively retained. At the same time, the degeneration of the subthalamic nucleus and the cerebellum prevents parkinsonism.The reason for cognitive decline may be related to the decrease in the network connection between the cerebellum and cerebral cortex in spinocerebellar ataxia type 2 patients.

Clinical features of corticobasal syndrome and associated chronic pain:analysis of 8 cases / 中华全科医师杂志

Objective:To investigate the clinical features and associated chronic pain in corticobasal syndrome (CBS).Methods:Clinical data of 8 patients diagnosed as probable CBS or possible CBS admitted to Beijing Hospital during January 2010 to June 2020 were retrospectively analyzed. The clinical information included sex, age, course of disease, chief complaint, neurological examination, blood biochemistry, tumor marker, infection and other laboratory tests; the neuropsychological evaluation included Mini-Mental State Examination (MMSE) scale and Hamilton Depression Scale (HAMD); the imaging studies included cranial magnetic resonance imaging (MRI) and/or 18F-Fluorodeoxyglucose positron emission tomography ( 18F-FDG PET). Results:The main clinical manifestations were asymmetrical movement disorders, including rigidity, tremor, myoclonus and abnormalities in posture and gait. Patients showed poor response to levodopa treatment. Among 8 patients, 7 had apraxia, 5 patients had alien hand, and 5 patients had various degrees of cognitive dysfunction. The cranial MRI demonstrated mild cerebral atrophy which was slightly more severe in the contralateral side of the initially affected limb in 7 of the 8 patients. The 18F-FDG PET scan revealed asymmetric decreased metabolism in the frontal, parietal, temporal, and occipital lobe, as well as in basal ganglia, which was more severe in the contralateral side of the initially affected limb in 5 of the 8 patients. Six of the 8 patients were associated with pain, including dystonic pain in 3 patients, neuropathic pain in 1 patient, musculoskeletal pain in 1 patient, and unexplained pain in 1 patient. Pain was the onset symptom in 1 patient and pain was relieved by taking levodopa in another patient. Conclusions:CBS is characterized by asymmetric dyskinesia and cognitive impairment, and often associated with apraxia, cortical sensory deficits, and alien limb. The MRI and PET are helpful for CBS diagnosis. Pain may be one of the common non-motor symptoms in CBS.