Fundamentals of deep brain stimulation for Parkinson's disease in clinical practice: part 2.

The field of neuromodulation has evolved significantly over the past decade. Developments include novel indications and innovations of hardware, software, and stimulation techniques leading to an expansion in scope and role of these techniques as powerful therapeutic interventions. In this review, which is the second part of an effort to document and integrate the basic fundamentals and recent successful developments in the field, we will focus on classic paradigms for electrode placement as well as new exploratory targets, mechanisms of neuromodulation using this technique and new developments, including focused ultrasound driven ablative procedures.

O campo da neuromodulação evoluiu significativamente na última década. Esse progresso inclui novas indicações e inovações de hardware, software e técnicas de estimulação, levando a uma expansão das áreas clínicas cobertas e no papel dessas técnicas como intervenções terapêuticas eficazes. Nesta revisão, que é a segunda parte de um esforço para documentar e integrar os fundamentos básicos e os desenvolvimentos recentes e bem-sucedidos no campo, vamos nos concentrar em paradigmas clássicos para colocação de eletrodos, bem como em novos alvos exploratórios, mecanismos de neuromodulação usados por esta técnica e novos desenvolvimentos, incluindo procedimentos ablativos orientados por ultrassom focalizado.

Fundamentals of deep brain stimulation for Parkinson's disease in clinical practice: part 1.

Deep brain stimulation (DBS) is recognized as an established therapy for Parkinson's disease (PD) and other movement disorders in the light of the developments seen over the past three decades. Long-term efficacy is established for PD with documented improvement in the cardinal motor symptoms of PD and levodopa-induced complications, such as motor fluctuations and dyskinesias. Timing of patient selection is crucial to obtain optimal benefits from DBS therapy, before PD complications become irreversible. The objective of this first part review is to examine the fundamental concepts of DBS for PD in clinical practice, discussing the historical aspects, patient selection, potential effects of DBS on motor and non-motor symptoms, and the practical management of patients after surgery.

Nas últimas três décadas, a estimulação cerebral profunda (ECP) se tornou um tratamento bem estabelecido para doença de Parkinson (DP) e outros transtornos do movimento. A eficácia a longo prazo na DP foi bem documentada para a melhora dos sintomas motores cardinais da DP e das complicações induzidas pelo uso do levodopa, como as flutuações motoras e as discinesias. O momento da seleção do paciente é crucial para se obter os benefícios ideais da ECP, antes que as complicações da DP se tornem irreversíveis. O objetivo desta primeira parte da revisão é examinar os conceitos fundamentais da ECP na prática clínica, discutindo os aspectos históricos, a seleção de pacientes, os potenciais efeitos da ECP nos sintomas motores e não motores da doença e o manejo prático dos pacientes após a cirurgia.

Fundamentals of deep brain stimulation for Parkinson's disease in clinical practice: part 1 / Princípios da estimulação cerebral profunda na doença de Parkinson na prática clínica: parte 1

Abstract Deep brain stimulation (DBS) is recognized as an established therapy for Parkinson's disease (PD) and other movement disorders in the light of the developments seen over the past three decades. Long-term efficacy is established for PD with documented improvement in the cardinal motor symptoms of PD and levodopa-induced complications, such as motor fluctuations and dyskinesias. Timing of patient selection is crucial to obtain optimal benefits from DBS therapy, before PD complications become irreversible. The objective of this first part review is to examine the fundamental concepts of DBS for PD in clinical practice, discussing the historical aspects, patient selection, potential effects of DBS on motor and non-motor symptoms, and the practical management of patients after surgery.

Resumo Nas últimas três décadas, a estimulação cerebral profunda (ECP) se tornou um tratamento bem estabelecido para doença de Parkinson (DP) e outros transtornos do movimento. A eficácia a longo prazo na DP foi bem documentada para a melhora dos sintomas motores cardinais da DP e das complicações induzidas pelo uso do levodopa, como as flutuações motoras e as discinesias. O momento da seleção do paciente é crucial para se obter os benefícios ideais da ECP, antes que as complicações da DP se tornem irreversíveis. O objetivo desta primeira parte da revisão é examinar os conceitos fundamentais da ECP na prática clínica, discutindo os aspectos históricos, a seleção de pacientes, os potenciais efeitos da ECP nos sintomas motores e não motores da doença e o manejo prático dos pacientes após a cirurgia.

Average annual cost of Parkinson's disease in a Brazilian multiethnic population.

INTRODUCTION: With the current demographic transition, it is estimated that by 2050 Brazil will have a population of 90 million people aged 60 years or more, and in parallel Parkinson's disease (PD) will bring a considerable economic burden to our society. Brazil is considered multiracial due to its colonization, generating important social and regional inequalities. Knowing the costs of the PD may aid to improve local public policies. However, in Brazil, no estimates of these values have been made so far. OBJECTIVES: To evaluate direct, indirect, and out-of-pocket costs in Brazilian people with PD (PwP). METHODS: Categorical and numerical data were collected through a customized and standardized cost-related-questionnaire from 1055 PwP nationwide, from 10 tertiary movement disorders centers across all Brazilian regions. RESULTS: The estimated average annual cost of PwP was US$ 4020.48. Direct and indirect costs accounted for 63% and 36% of the total, respectively, and out-of-pocket costs were 49%. There were no evidence of differences in the total cost of PD across the regions of the country; however, differences were reported between the stages of the Hoehn and Yahr scale (H&Y). CONCLUSION: This data suggests a considerable burden of PD for Brazilian society in general, not only for the public health system, but mainly for those with PD.

Evaluation of dopamine transporter density in healthy Brazilians using Tc-99m TRODAT-1 SPECT.

ABSTRACT: The presynaptic dopamine transporter (DAT) modulates the uptake of dopamine by regulating its concentration in the central nervous system. We aimed to evaluate the DAT binding potential (DAT-BP) in a sample of healthy Brazilians through technetium-99 metastable TRODAT-1 single-photon emission computed tomography imaging.We selected 126 healthy individuals comprising 72 men and 54 women, aged 18 to 80 years. We conducted semi-quantitative evaluation in transaxial slices, following which we identified the regions of interest in the striatal region using the occipital lobe as a region of non-specific DAT-BP.We found a decrease in DAT-BP in healthy individuals aged over 30 years, culminating in a 42% mean reduction after 80 years. There was no difference in the decrease by age group between the right (linear regression test [R2] linear = 0.466) and left striatum (R2 linear = 0.510). Women presented a higher DAT-BP than men (women: R2 linear = 0.431; men: R2 linear = 0.457); nonetheless, their decrease by age group was equal to that in men.Our study sheds light on important DAT-BP findings in healthy Brazilian subjects. Our results will facilitate understanding of brain illnesses that involve the dopamine system, such as neuropsychiatric disorders.

A Real-World Study of Cerebral 99mTc-TRODAT-1 Single-Photon Emission Computed Tomography (SPECT) Imaging of the Dopamine Transporter in Patients with Parkinson Disease from a Tertiary Hospital in Brazil.

BACKGROUND Studies on the routine clinical use of dopamine transporter (DAT) imaging have largely been conducted in Europe and the United States. In this real-world study, we investigated the use of cerebral 99mTc-TRODAT-1 SPECT imaging of DAT in patients with Parkinson disease (PD) at a tertiary hospital in Brazil. MATERIAL AND METHODS We included 119 patients with suspected PD or clinically unclear parkinsonism who underwent brain scintigraphy with 99mTc-TRODAT-1 during a 3-year period. Additionally, a brief interview was conducted with the physician who requested the scan to determine the usefulness of the method in clinical decision-making. RESULTS Regarding the scan requests, most were intended to evaluate or confirm dopaminergic denervation (69%), distinguish PD from essential tremor (10%), or distinguish degenerative parkinsonism from drug-induced parkinsonism (6%). Data analysis showed that scintigraphy with 99mTc-TRODAT-1 was useful in 85% of cases, changing the management of 75% of the patients who underwent a scan. The majority of physicians who requested the scan were neurologists, and 54% were self-reported movement disorder specialists. An inappropriate use of DAT imaging was seen in 5% of cases. CONCLUSIONS This study demonstrated that brain scintigraphy with the DAT ligand 99mTc-TRODAT-1 may influence diagnostic or therapeutic interventions, meaning that Brazilian physicians who requested the exam have taken in vivo DAT results into account at the time of clinical decision-making.

Impaired brain dopamine transporter in chemobrain patients submitted to brain SPECT imaging using the technetium-99m labeled tracer TRODAT-1.

PURPOSE: "Chemobrain" is a medical secondary effect of cancer chemotherapy treatment characterized by a general decline in cognition affecting visual and verbal memory, attention, complex problem-solving skills, and motor function. Dopamine (DA) central nervous system neurotransmitters serve an important role in cognition, and changes in DA could potentially explain impaired cognition associated with chemotherapy. Therefore, our objective was to assess in vivo dopaminergic dysfunction in the central nervous system (CNS) of a group of female breast cancer survivors with cognitive impairment following chemotherapy. METHODS: Twenty-eight women reporting chemobrain were recruited for this study and compared to 22 healthy reference women. Striatal dopamine transporter (DAT) binding ratio was determined by 99mTc-TRODAT-1 (a highly selective radiotracer for DAT in the dorsal striatum) single-photon emission computed tomography and a quantitative evaluation was obtained by DatQUANT™ software (GE Healthcare). The DAT binding ratio (BRDAT) in the patient and control groups was compared using the Student's t test, a multivariate analysis of variance (MANOVA) was used to compare age, years of schooling and BRDAT. The relationship between continuous variables, such as cognitive impairment and BRDAT was assessed using Pearson correlation test. RESULTS: There was a difference in BRDAT between the chemobrain patients and control group. Patients had statistically significant (p < 0.05) lower concentrations of the radiopharmaceutical in the striatum. CONCLUSIONS: We identified a significant dopaminergic decrease in all regions of the dorsal striatum within the patients reporting cognitive dysfunction after chemotherapy. Therefore, our results indicate a possible role of dopamine transporter in the physiopathology of chemobrain, even out of the acute phase of symptoms.

Average annual cost of Parkinson's disease in São Paulo, Brazil, with a focus on disease-related motor symptoms.

BACKGROUND: Although Parkinson's disease is the second most prevalent neurodegenerative disease worldwide, its cost in Brazil - South America's largest country - is unknown. OBJECTIVE: The goal of this study was to calculate the average annual cost of Parkinson's disease in the city of São Paulo (Brazil), with a focus on disease-related motor symptoms. SUBJECTS AND METHODS: This was a retrospective, cross-sectional analysis using a bottom-up approach (ie, from the society's perspective). Patients (N=260) at two tertiary public health centers, who were residents of the São Paulo metropolitan area, completed standardized questionnaires regarding their disease-related expenses. We used simple and multiple generalized linear models to assess the correlations between total cost and patient-related, as well as disease-related variables. RESULTS: The total average annual cost of Parkinson's disease was estimated at US$5,853.50 per person, including US$3,172.00 in direct costs (medical and nonmedical) and US$2,681.50 in indirect costs. Costs were directly correlated with disease severity (including the degree of motor symptoms), patients' age, and time since disease onset. CONCLUSION: In this study, we determined the cost of Parkinson's disease in Brazil and observed that disease-related motor symptoms are a significant component of the costs incurred on the public health system, patients, and society in general.

Systematic Review and Critical Analysis of Cost Studies Associated with Parkinson's Disease.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease worldwide, affecting more than four million people. Typically, it affects individuals above 45, when they are still productive, compromising both aging and quality of life. Therefore, the cost of the disease must be identified, so that the use of resources can be rational and efficient. Additionally, in Brazil, there is a lack of research on the costs of neurodegenerative diseases, such as PD, a gap addressed in this study. This systematic review critically addresses the various methodologies used in original research around the world in the last decade on the subject, showing that costs are hardly comparable. Nonetheless, the economic and social impacts are implicit, and important information for public health agents is provided.

How do demographic transitions and public health policies affect patients with Parkinson's disease in Brazil?

Brazil is currently experiencing a significant demographic transition characterized by a decrease in fertility rates and an exponential increase in the number of elderly citizens, which presents a special challenge for the health care professionals. More than other portions of the population, the elderly are most commonly affected by chronic diseases such as Parkinson's disease. Policymakers contend that Brazil is reasonably well-prepared regarding elderly health care, with policies that aim to ensure the quality of life and the well-being of this portion of the population. However, what happens in practice falls short of what the Brazilian Constitution sets forth. Specifically, there is a clear contradiction between what the law recognizes as being a citizen's rights and the implementation of guidelines. Because health financing in Brazil remains relatively low, the civil society tries to fill in the gaps as much as possible in the treatment of elderly patients suffering from chronic diseases such as Parkinson's disease. In this review, we outline the current legislation in Brazil regarding the elderly and in particular, patients with Parkinson's disease, in the context of a rapidly aging population.

PET-CT as an Alternative to Fiducial Markers Guidance in Liver Metastasis Treatment.

The liver is the organ most commonly affected by colorectal cancer metastasis. Currently, liver resection is the treatment of choice, but in cases where it is not possible, intensity-modulated radiation therapy is an alternative. We report the case of a 57-year-old woman whose colorectal carcinoma metastasized to the liver. She was referred for implantation of fiducial markers for intensity-modulated radiation therapy planning. PET-CT stands out as an additional tool for distinguishing metabolically active tumor tissue from other tissues, ensuring effective introduction of percutaneous fiducial markers, especially in cases where use of conventional imaging techniques is limited.

Presence or absence of cognitive complaints in Parkinson's disease: mood disorder or anosognosia?

We intended to evaluate whether non-demented Parkinsons's disease (PD) patients, with or without subjective cognitive complaint, demonstrate differences between them and in comparison to controls concerning cognitive performance and mood. We evaluated 77 subjects between 30 and 70 years, divided as follows: PD without cognitive complaints (n = 31), PD with cognitive complaints (n = 21) and controls (n = 25). We applied the following tests: SCOPA-Cog, Trail Making Test-B, Phonemic Fluency, Clock Drawing Test, Boston Naming Test, Neuropsychiatric Inventory, Hospital Anxiety and Depression Scale (HADS) and Beck Depression Inventory. PD without complaints presented lower total score on Scales for outcome of Parkinson's disease-cognition as compared to controls (p = 0.048). PD with complaints group showed higher scores on HADS (p = 0.011). PD without complaints group showed poorer cognitive performance compared to controls, but was similar to the PD with complaints group. Moreover, this group was different from the PD without complaints and control groups concerning mood.

Presence or absence of cognitive complaints in Parkinson's disease: mood disorder or anosognosia? / Presença ou ausência de queixas cognitivas na doença de Parkinson: transtorno de humor ou anosognosia?

ABSTRACT We intended to evaluate whether non-demented Parkinsons’s disease (PD) patients, with or without subjective cognitive complaint, demonstrate differences between them and in comparison to controls concerning cognitive performance and mood. We evaluated 77 subjects between 30 and 70 years, divided as follows: PD without cognitive complaints (n = 31), PD with cognitive complaints (n = 21) and controls (n = 25). We applied the following tests: SCOPA-Cog, Trail Making Test-B, Phonemic Fluency, Clock Drawing Test, Boston Naming Test, Neuropsychiatric Inventory, Hospital Anxiety and Depression Scale (HADS) and Beck Depression Inventory. PD without complaints presented lower total score on Scales for outcome of Parkinson’s disease-cognition as compared to controls (p = 0.048). PD with complaints group showed higher scores on HADS (p = 0.011). PD without complaints group showed poorer cognitive performance compared to controls, but was similar to the PD with complaints group. Moreover, this group was different from the PD without complaints and control groups concerning mood.

RESUMO Avaliar se pacientes com doença de Parkinson (DP) sem demência, com ou sem queixa cognitiva subjetiva, demonstram diferenças entre eles e comparativamente aos controles relativos a desempenho cognitivo e humor. Avaliados 77 indivíduos entre 30 e 70 anos: PD sem queixas cognitivas (n = 31), PD com queixas cognitivas (n = 21) e controles (n = 25). Testes aplicados: SCOPA-cognição, Trail Making Test-B, Fluência Fonêmica, Teste do Relógio, Teste Nominativo de Boston, Inventário Neuropsiquiátrico, Escala Hospitalar de Depressão e Ansiedade (HADS)e Inventário de Depressão de Beck. PD sem queixas apresentaram menor pontuação total na SCOPA-cognição, comparativamente aos controles (p = 0,048). Por outro lado, PD com queixas apresentaram maior pontuação no HADS (p = 0,011) em comparação aos controles. O grupo PD sem queixas mostrou pior desempenho cognitivo em comparação aos controles, mas foi semelhante ao PD com queixas. Este grupo foi diferente dos grupos PD sem queixas e controle em relação ao humor.

Patients with essential tremor can have manual dexterity and attention deficits with no impairments in other cognitive functions.

Essential tremor (ET) was long believed to be a monosymptomatic disorder. However, studies have evidenced structural changes and attention is now being focused on non-motor symptoms. The objective of the study is to describe and compare ET patients with control groups according to their cognitive functions, and secondarily, to compare their sociodemographic characteristics and other clinical features. All participants were assessed using the Fahn-Tolosa-Marin Tremor Rating Scale for the severity of tremor; a neuropsychological assessment battery and a screening questionnaire for mood and anxiety symptoms. There were no significant age and gender differences between all groups. As for neuropsychological assessment results, a significant difference was found only in the Pegboard test. We also found a significant negative correlation between a poorer cognitive test results and disease severity and a significant differences regarding depression or anxiety symptoms in patients with ET. The study results suggest that patients with ET have impaired manual dexterity and attention.

Patients with essential tremor can have manual dexterity and attention deficits with no impairments in other cognitive functions / Pacientes com tremor essencial podem apresentar prejuízo na destreza manual e déficit de atenção sem prejuízo em outras áreas da cognição

ABSTRACT Essential tremor (ET) was long believed to be a monosymptomatic disorder. However, studies have evidenced structural changes and attention is now being focused on non-motor symptoms. The objective of the study is to describe and compare ET patients with control groups according to their cognitive functions, and secondarily, to compare their sociodemographic characteristics and other clinical features. All participants were assessed using the Fahn-Tolosa-Marin Tremor Rating Scale for the severity of tremor; a neuropsychological assessment battery and a screening questionnaire for mood and anxiety symptoms. There were no significant age and gender differences between all groups. As for neuropsychological assessment results, a significant difference was found only in the Pegboard test. We also found a significant negative correlation between a poorer cognitive test results and disease severity and a significant differences regarding depression or anxiety symptoms in patients with ET. The study results suggest that patients with ET have impaired manual dexterity and attention.

RESUMO O tremor essencial (TE) era considerado como um transtorno monossintomático. Contudo estudos tem demonstrado alterações anatômicas despertando o interesse para sintomas não-motores.O objetivo do estudo é descrever e comparar pacientes com grupos controles segundo suas funções cognitivas, e secundariamente, comparar suas características demográficas e outros sintomas clínicos. Todos os participantes foram submetidos à escala de Fahn, Tolosa e Marin para avaliação da intensidade do tremor, a uma bateria neuropsicológica e a um questionário para detecção de transtorno de humor e ansiedade. Não houve diferença significativa na idade e gênero entre todos os grupos. Quanto ao resultado da avaliação neuropsicológica, foi encontrado uma diferença significativa apenas no Test Pegboard. Nós também encontramos uma correlação negativa no desempenho dos testes cognitivos e intensidade do tremor, presença de sintomas depressivos e ansiosos. Os resultados deste trabalho sugerem que pacientes com TE apresentem alteração na destreza manual e na atenção.

Dopamine transporter imaging using 99mTc-TRODAT-1 SPECT in Parkinson's disease.

BACKGROUND: Although the decrease in striatal dopamine transporter (DAT) density has been described in North American, European, and Asian Parkinson's disease (PD) patients, studies on this issue are required in the rest of the world. This study examined the diagnostic utility of DAT imaging in Brazilian PD patients. MATERIAL/METHODS: Twenty PD patients (13 males, 7 females, median age: 62 years, median age at disease onset: 56 years, median disease duration: 5 years, and median UPDRS-III score: 29) and 9 age- and sex-matched healthy subjects underwent single-photon emission computerized tomography (SPECT) using 99mTc-TRODAT-1. RESULTS: PD patients showed a significant decrease in the striatum, caudate nucleus, and putamen DAT densities compared with data from healthy subjects. Striatal 99mTc-TRODAT-1 bindings had the highest diagnostic accuracy compared to those estimates from caudate nucleus and putamen. For the diagnosis of PD, a striatal 99mTc-TRODAT-1 binding cut-off value of 0.90 was associated with a sensitivity of 100% and a specificity of 89%. There was no significant difference between striatal 99mTc-TRODAT-1 binding values provided by different readers, contrary to 99mTc-TRODAT-1 binding estimates in the caudate nucleus. CONCLUSIONS: Striatal DAT imaging using 99mTc-TRODAT-1 can be considered a marker for differentiating PD patients from healthy individuals, with a good interobserver reproducibility.

Depression increases in patients with Parkinson?s disease according to the increasing severity of the cognitive impairment.

OBJECTIVE: To test the hypothesis that severity of cognitive impairment modifies the association between depression and Parkinson's disease (PD). METHOD: One-phase population-based door-to-door surveys. This is a secondary analysis of 1,451 people aged 65 years and older with cognitive impairment living in defined catchment areas. Depression was estimated according to ICD-10, self-reported PD, disability according to WHODAS-II and cognitive status according to the CSI-D. RESULTS: The mean age of the sample was 79.3 years old and most (69%) were women. Of the total sample, 16.1% had depression and it was significantly higher among participants with PD. There was an increase on the ORs of the association between depression and PD with decreased scores in the cognitive test (Adjusted OR from 0.98 to 8.04). CONCLUSION: The association between depression and PD increases with the severity of the cognitive impairment.

Depression increases in patients with Parkinson?s disease according to the increasing severity of the cognitive impairment / Em pacientes com doença de Parkinson, a depressão aumenta de acordo com o aumento da gravidade do comprometimento cognitivo

Objective : To test the hypothesis that severity of cognitive impairment modifies the association between depression and Parkinson’s disease (PD). Method : One-phase population-based door-to-door surveys. This is a secondary analysis of 1,451 people aged 65 years and older with cognitive impairment living in defined catchment areas. Depression was estimated according to ICD-10, self-reported PD, disability according to WHODAS-II and cognitive status according to the CSI-D. Results : The mean age of the sample was 79.3 years old and most (69%) were women. Of the total sample, 16.1% had depression and it was significantly higher among participants with PD. There was an increase on the ORs of the association between depression and PD with decreased scores in the cognitive test (Adjusted OR from 0.98 to 8.04). Conclusion : The association between depression and PD increases with the severity of the cognitive impairment. .

Objetivo : Testar a hipótese que a gravidade do prejuízo cognitivo modifica a associação entre depressão e doença de Parkinson (DP). Método : Estudo populacional através da análise secundária de 1.451 pessoas com idade maior ou igual a 65 anos com prejuízo cognitivo que residiam em áreas de abrangência definidas. A depressão foi estimada de acordo com a CID-10, auto-relato de DP, incapacidade conforme a WHODAS-II e nível cognitvo de acordo com a CSI-D. Resultado : A média de idade foi 79,3 anos, predominaram as mulheres (69%). Do total de indivíduos, 16,1% tinham depressão, significantemente maior entre os participantes com DP. Houve aumento gradativo na OR relativa à associação entre depressão e DP com a diminuição do escore no teste cognitivo (OR ajustado variou de 0,98 a 8,04). Conclusão : A associação entre depressão e DP parece aumentar com a gravidade do prejuízo cognitivo. .