Transitioning from Subtyping to Precision Medicine in Parkinson's Disease: A Purpose-Driven Approach.

The International Parkinson and Movement Disorder Society (MDS) created a task force (TF) to provide a critical overview of the Parkinson's disease (PD) subtyping field and develop a guidance on future research in PD subtypes. Based on a literature review, we previously concluded that PD subtyping requires an ultimate alignment with principles of precision medicine, and consequently novel approaches were needed to describe heterogeneity at the individual patient level. In this manuscript, we present a novel purpose-driven framework for subtype research as a guidance to clinicians and researchers when proposing to develop, evaluate, or use PD subtypes. Using a formal consensus methodology, we determined that the key purposes of PD subtyping are: (1) to predict disease progression, for both the development of therapies (use in clinical trials) and prognosis counseling, (2) to predict response to treatments, and (3) to identify therapeutic targets for disease modification. For each purpose, we describe the desired product and the research required for its development. Given the current state of knowledge and data resources, we see purpose-driven subtyping as a pragmatic and necessary step on the way to precision medicine. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Levodopa versus levodopa sparing in early parkinson's disease: can we meet halfway?

Monotherapy is the recommended initial treatment for early Parkinson's disease. The pharmacological options for initial treatment include dopaminergic agonists, monoamine oxidase B inhibitors, and levodopa formulations. Several factors should be considered when selecting the optimal treatment, such as disease severity, disease duration, age, activity level, and the risk of developing motor and non-motor complications. Early evidence on the potential role of levodopa formulations in the risk of dyskinesia led to levodopa aversion in the late 1990s and early 2000s, favoring the use of levodopa-sparing options like dopamine agonists. This shift resulted in an increase in behavioral adverse effects, such as impulse control disorders, leading to a subsequent dopamine agonist aversion in the mid-2000s. This review aims to provide a comprehensive evaluation of the existing literature regarding the benefits and drawbacks of levodopa versus levodopa-sparing strategies in drug-naive early-stage Parkinson's disease.

Levodopa Dose Equivalency in Parkinson's Disease: Updated Systematic Review and Proposals.

BACKGROUND: To compare drug regimens across clinical trials in Parkinson's disease (PD) conversion formulae between antiparkinsonian drugs have been developed. These are reported in relation to levodopa as the benchmark drug in PD pharmacotherapy as 'levodopa equivalent dose' (LED). Currently, the LED conversion formulae proposed in 2010 by Tomlinson et al. based on a systematic review are predominantly used. However, new drugs with established and novel mechanisms of action and novel formulations of longstanding drugs have been developed since 2010. Therefore, consensus proposals for updated LED conversion formulae are needed. OBJECTIVES: To update LED conversion formulae based on a systematic review. METHODS: The MEDLINE, CENTRAL, and Embase databases were searched from January 2010 to July 2021. Additionally, in a standardized process according to the GRADE grid method, consensus proposals were issued for drugs with scarce data on levodopa dose equivalency. RESULTS: The systematic database search yielded 3076 articles of which 682 were eligible for inclusion in the systematic review. Based on these data and the standardized consensus process, we present proposals for LED conversion formulae for a wide range of drugs that are currently available for the pharmacotherapy of PD or are expected to be introduced soon. CONCLUSIONS: The LED conversion formulae issued in this Position Paper will serve as a research tool to compare the equivalence of antiparkinsonian medication across PD study cohorts and facilitate research on the clinical efficacy of pharmacological and surgical treatments as well as other non-pharmacological interventions in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Experience with Creutzfeldt-Jakob disease in a single referral center in Mexico. Case series.

INTRODUCTION: Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and fatal central nervous system disease caused by prions. OBJECTIVE: To present the main clinical and paraclinical characteristics of patients with probable CJD in a referral center of Latin America. METHODS: Retrospective study of patients diagnosed with rapidly progressive dementia between 2014 and 2019. Clinical, demographic, electroencephalogram, magnetic resonance imaging, and 14-3-3 protein characteristics were included, as well as positron-emission tomography (PET) data when available. RESULTS: Twenty-four patients met the criteria for sporadic CJD (75% were women). Mean age was 59.29 ± 11.67 years, while mean disease duration from symptom onset to hospital admission was 7.41 ± 6.54 months. The most common first symptom was behavioral changes (41.7%). Delta wave complexes prevailed (54.2%) on electroencephalogram, cortical hyperintensity (83.3%) on magnetic resonance and frontal hypometabolism (37.5%) on PET. Seven cases showed positive total Tau; five, positive 14-3-3 protein; and three, positive phosphorylated tau on cerebrospinal fluid analysis. CONCLUSIONS: There is significant clinical heterogeneity regarding initial symptoms. Auxiliary test findings were consistent with those of other series.

INTRODUCCIÓN: La enfermedad de Creutzfeldt-Jakob (ECJ) es una enfermedad del sistema nervioso central rápidamente progresiva y mortal causada por priones. OBJETIVO: Presentar las principales características clínicas y paraclínicas de pacientes con probable ECJ en un centro de referencia de América Latina. MÉTODOS: Estudio retrospectivo de pacientes diagnosticados con demencia rápidamente progresiva entre 2014 y 2019. Se incluyeron características clínicas, demográficas, del electroencefalograma, imágenes por resonancia magnética, proteína 14-3-3 y tomografía por emisión de positrones (PET), cuando estaba disponible. RESULTADOS: Veinticuatro pacientes cumplieron con los criterios de ECJ esporádica (75 % mujeres), la edad media fue de 59.29 ± 11.67 años, la duración de la enfermedad desde el inicio de los síntomas hasta el ingreso hospitalario fue de 7.41 ± 6.54 meses y las primeras manifestaciones más comunes fueron las alteraciones del comportamiento (41.7 %). Los complejos de ondas delta prevalecieron en el electroencefalograma (54.2 %), la hiperintensidad cortical en la resonancia magnética (83.3 %) y el hipometabolismo frontal en la PET (37.5 %). En el análisis del líquido cefalorraquídeo, siete casos mostraron proteína tau total positiva; cinco, proteína 14-3-3 positiva; y tres, proteína tau hiperfosforilada positiva. CONCLUSIONES: Existe importante heterogeneidad clínica en cuanto a los síntomas iniciales. Los hallazgos de las pruebas auxiliares coincidieron con los de otras series.

Worldwide barriers to genetic testing for movement disorders.

BACKGROUND AND PURPOSE: Despite enormous advances in identifying genetic variants responsible for many neurological diseases, access to genetic testing may be limited in clinical practice. The objective of this study was to assess worldwide access to genetic tests for movement disorders and factors impacting their utilization. METHODS: The Rare Movement Disorders Study Group of the International Parkinson and Movement Disorder Society designed an online survey electronically mailed to all 7815 members. RESULTS: Survey data completed by 1269 participants from 109 countries were analysed. Limited access to geneticists and genetic counsellors was reported in many world regions compared to Europe and North America. Availability of genetic testing was limited, with rates of access lower than 50%. Genetic testing for chorea was the most commonly available. For parkinsonism, dystonia, ataxia, hereditary spastic paraplegias and metabolic disorders, there was limited access to genetic testing in all countries compared to Europe and North America, with significant differences found for Africa, Central/South America, Asia. In many regions, genetic testing was supported by either private or public funding. Genetic testing was free of charge in Europe according to 63.5% of respondents. In North America, Africa, Central/South America, Asia and the Middle East access to free of charge genetic testing was by far significantly lower compared to Europe. CONCLUSIONS: This survey highlights difficulties in accessing genetic testing and individuals with expertise in genetics at the worldwide level. In addition, major disparities in genetic testing amongst world regions are highlighted, probably due to a variety of factors including financial barriers.

Association Between Somatization and Nonmotor Symptoms Severity in People With Parkinson Disease.

OBJECTIVE: To assess the frequency of somatization and its association with motor, nonmotor symptoms, and quality of life in persons with Parkinson disease (PD). METHODS: A cross-sectional case-control study was carried out. Assessments included the List of 90 Symptoms somatic factor (SCL-90-R SOM), Movement Disorder Society Unified Parkinson's Ratings Scale (MDS-UPDRS), Non-Motor Symptom Scale (NMSS), Montreal Cognitive Assessment (MoCA), and Parkinson Questionnaire-8 (PDQ-8). RESULTS: A total 93 persons with PD and 93 controls were included. Somatization within the PD group was 2 times more frequent compared to the control group (43% vs 21.5%, P = .003). Persons with PD had higher NMSS total scores (48.6 ± 42.6 vs 28.3 ± 30.4, P = .001). Patients with PD with somatization had worst MDS-UPDRS, NMSS, MoCA, and PDQ-8 (all P < .05). CONCLUSION: Somatization is more frequent in persons with PD compared to healthy controls. Somatization in PD is associated with nonmotor symptoms and worst quality of life.

Association between cardiometabolic comorbidities and Parkinson's disease in a Mexican population.

BACKGROUND: The prevalence of Parkinson's disease (PD) increases as the population ages. Studies have shown that some cardiometabolic comorbidities could be associated with risk or protection against developing PD. A retrospective case-control study was carried out to analyze the relationship between PD and cardiometabolic comorbidities. MATERIAL AND METHODS: Subjects with PD and controls without PD were consecutively recruited. Data on type 2 diabetes mellitus, systemic arterial hypertension (SAH), dyslipidemia and body mass index were collected. Logistic regression analyses were carried out. RESULTS: A total of 781 subjects with PD (56.5% males) and 1,000 controls (44.4% males) were included. After adjusting for age and gender, SAH was found as an independent risk factor (OR: 1.32; 95% CI: 1.05-1.67; p = 0.02), and obesity as a protective factor (OR: 0.72; 95% CI: 0.56-0.93; p = 0.01). CONCLUSIONS: Subjects with SAH had a higher risk of having PD, while obese subjects had a lower risk of having PD. The relationship between cardiometabolic disease, its treatment, and PD etiopathogenesis appears to be extremely complex given the amount of contradictory data.

ANTECEDENTES: La prevalencia de la enfermedad de Parkinson (EP) aumenta a medida que la población envejece. Los estudios han demostrado que algunas comorbilidades cardiometabólicas pudieran estar asociadas con el riesgo o la protección de desarrollar la EP. Se realizó un estudio retrospectivo de casos y controles para analizar la relación entre la EP y las comorbilidades cardiometabólicas. MATERIAL Y MÉTODOS: Se reclutaron sujetos con EP y controles sin EP de forma consecutiva. Se recolectaron datos sobre diabetes mellitus tipo 2, hipertensión arterial sistémica (HTA), dislipidemia e índice de masa corporal. Se llevó a cabo análisis de regresión logística. RESULTADOS: Se incluyeron un total de 781 personas con EP (56,5% hombres) y 1,000 controles (44,4% hombres). Después de ajustar por edad y sexo, la HTA se encontró como factor de riesgo independiente (OR 1.32, IC 95% 1.05-1.67, p = 0.02) y la obesidad como factor protector (OR 0.72, IC 95% 0.56-0.93, p = 0.01). CONCLUSIONES: Los sujetos con HTA tienen un mayor riesgo de tener EP; mientras que los sujetos obesos tienen un menor riesgo de tener EP. La relación entre la enfermedad cardiometabólica, su tratamiento y etiopatogenia de la EP parece ser extremadamente compleja dada la cantidad de datos contradictorios.

Malnutrition and Associated Motor and Non-motor Factors in People with Parkinson's Disease.

BACKGROUND: People with Parkinson's disease (PwP) are at higher risk of developing malnutrition. Several factors have been suggested to be involved including motor symptoms, non-motor symptoms, and treatment-related complications. OBJECTIVE: The objective of the study was to analyze the combined effect of motor, non-motor, and pharmacological factors in the risk of malnutrition in PwP. METHODS: Eighty-seven consecutive PwP were included in the study. Clinical data and pharmacological treatment were collected. Nutritional status was assessed using the Mini-Nutritional Assessment (MNA) questionnaire. Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Non-motor Symptoms Scale (NMSS), Hamilton Depression Rating Scale HAM-D, and Montreal Cognitive Assessment were applied. RESULTS: Thirty (34.4%) PwP were at risk of malnutrition and seven had malnutrition (8%). Abnormal nutritional status was associated with lower education, higher MDSUPDRS Parts I, II, and III and total scores, and higher scores in the NMSS domain of sleep disorders and fatigue. MDS-UPDRS motor score remained as a determinant of abnormal nutritional status, defined as MNA < 23.5, with an odds ratio 1.1 (95% confidence interval 1.01-1.10, p = 0.02). CONCLUSION: The main factor associated with nutritional status was severity of the motor symptoms as assessed by the MDS-UPDRS Part III. Non-motor symptoms and treatment-related complications were not associated with malnutrition.

Neurological manifestations in coronavirus disease 2019.

Coronavirus disease 2019 (COVID-19), an infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently hitting the world in the form of a pandemic. Given that some reports suggest that this infection can also occur with neurologic manifestations, this narrative review addresses the basic and clinical aspects concerning the nervous system involvement associated with this disease. More than one third of patients hospitalized for COVID-19 can present with both central and peripheral neurological manifestations. The former include dizziness and headache, while the latter include taste and smell disturbances. Other reported neurological manifestations are cerebrovascular disease and epileptic seizures. According to published reports, neurological disorders are not uncommon in COVID-19 and can sometimes represent the first manifestation of the disease; therefore, neurologists should consider this diagnostic possibility in their daily practice. Since maybe not all COVID-19 neurological manifestations are due to SARS-CoV-2 direct effects, it is important to monitor the rest of the clinical parameters such as, for example, oxygen saturation. Similarly, follow-up of patients is advisable, since whether neurological complications may develop lately is thus far unknown.

La enfermedad del coronavirus 2019 (COVID-19), infección causada por el coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2), actualmente afecta al mundo en forma de una pandemia. Debido a que algunos reportes apuntan a que esta infección puede cursar también con manifestaciones neurológicas, en esta revisión narrativa se abordan los aspectos básicos y clínicos concernientes a la afectación del sistema nervioso por esta enfermedad. Más de un tercio de los pacientes hospitalizados por COVID-19 pueden presentar manifestaciones neurológicas, tanto centrales como periféricas. Entre las primeras se encuentran el mareo y la cefalea; y entre las segundas, las alteraciones del gusto y el olfato. Otras manifestaciones neurológicas reportadas son la enfermedad vascular cerebral y las crisis epilépticas. Según los informes publicados, los padecimientos neurológicos no son infrecuentes en COVID-19 y en ocasiones pueden representar la primera manifestación de la enfermedad, de modo que los neurólogos deberán considerar esta posibilidad diagnóstica en su práctica cotidiana. Dado que no todas las manifestaciones neurológicas de COVID-19 pudieran deberse a efectos directos de SARS-CoV-2, es importante monitorear el resto de los parámetros clínicos, por ejemplo, la oxigenación. De igual forma, es recomendable el seguimiento de los pacientes, ya que hasta el momento se ignora si las complicaciones neurológicas pueden desarrollarse tardíamente.

Factores asociados con deterioro cognitivo en una cohorte mexicana multicéntrica de Parkinson: estudio transversal comparativo.

INTRODUCTION: Cognitive impairment is common in Parkinson's disease and represents a risk for dementia. Identifying associated factors will help implement early interventions and study its progression. OBJECTIVE: To identify factors associated with cognitive impairment. METHOD: Cross-sectional study of 306 subjects with Parkinson's disease who were assessed for 12 months. Demographics and clinical variables were analyzed as explanatory variables, and cognitive impairment as outcome variable. Significant variables were used to construct a cognitive impairment predictive model. RESULTS: Cognitive impairment was reported in 43.8%. Female gender (p = 0.001, odds ratio [OR] = 1.77), age at diagnosis (p < 0.001, mean deviation [MD] = 5.7), level of education (p < 0.001, MD = -2.9), disease duration (p = 0.003, MD = 1.7), MDS-UPDRS part III score (p < 0.001, MD = 9.7), presence of anxiety (p = 0.007, OR = 2.11), hallucinations (p = 0.029, OR = 2.27) and freezing of gait (p = 0.048, OR = 1.91) were predictors for cognitive impairment. The use of type B monoamine oxidase inhibitors was associated with less cognitive impairment (p = 0.001). CONCLUSIONS: Predictive factors that were consistent with those previously reported were identified. Prospective studies are required in order to clarify the effect of type B monoamine oxidase inhibitors on cognition.

INTRODUCCIÓN: El deterioro cognitivo en Parkinson es común y representa un riesgo para demencia. Identificar los factores asociados ayudará a implementar intervenciones tempranas y estudiar la progresión del deterioro cognitivo. OBJETIVO: Identificar factores asociados con deterioro cognitivo. MÉTODO: Estudio transversal de 306 sujetos con Parkinson evaluados durante los últimos 12 meses. Se estudiaron variables demográficas y clínicas como explicativas y el deterioro cognitivo como desenlace. Las variables significativas se utilizaron para construir un modelo predictor de deterioro cognitivo. RESULTADOS: El 43.8 % reportó deterioro cognitivo. El sexo femenino (p = 0.001, RM = 1.77), edad al diagnóstico (p < 0.001, desviación media [DM] 5.7), escolaridad (p < 0.001, DM −2.9), duración de enfermedad (p = 0.003, DM 1.7), puntuación en MDS-UPDRS parte III (p < 0.001, DM 9.7), presencia de ansiedad (p = 0.007, RM = 2.11), de alucinaciones (p = 0.029, RM = 2.27) y congelamientos de la marcha (p = 0.048, RM = 1.91) fueron predictores para deterioro cognitivo. El uso de inhibidores ­monoamina-oxidasa tipo B se asoció con menor deterioro cognitivo (p = 0.001). CONCLUSIONES: Se identificaron factores predictores consistentes con lo reportado previamente. Se requieren estudios prospectivos para aclarar el efecto de los inhibidores monoamina-oxidasa tipo B en la cognición.

Treatable inherited rare movement disorders.

There are many rare movement disorders, and new ones are described every year. Because they are not well recognized, they often go undiagnosed for long periods of time. However, early diagnosis is becoming increasingly important. Rapid advances in our understanding of the biological mechanisms responsible for many rare disorders have enabled the development of specific treatments for some of them. Well-known historical examples include Wilson disease and dopa-responsive dystonia, for which specific and highly effective treatments have life-altering effects. In recent years, similarly specific and effective treatments have been developed for more than 30 rare inherited movement disorders. These treatments include specific medications, dietary changes, avoidance or management of certain triggers, enzyme replacement therapy, and others. This list of treatable rare movement disorders is likely to grow during the next few years because a number of additional promising treatments are actively being developed or evaluated in clinical trials. © 2017 International Parkinson and Movement Disorder Society.

Diagnostic Utility of [11C]DTBZ Positron Emission Tomography In Clinically Uncertain Parkinsonism: Experience of a Single Tertiary Center.

BACKGROUND: The use of single-photon emission computed tomography and positron emission tomography (PET) has proven to be helpful in differentiating Parkinson's disease (PD) from other movement disorders with a sensitivity of up to 95%. OBJECTIVE: The objective of this study was to determine the accuracy of [11C]DTBZ PET imaging in patients with clinically uncertain parkinsonism from a tertiary referral center in Mexico City. MATERIALS AND METHODS: Patients who underwent [11C]DTBZ PET brain scan due to clinically uncertain parkinsonism where divided into two groups: PD or non-PD. A scan was considered positive when visual assessment revealed a decrease in [11C]DTBZ uptake typical for PD; a scan was considered negative when visual assessment showed no decrease in [11C]DTBZ uptake or showed a decrease in tracer uptake in a non-PD pattern. Sensitivity, specificity, and positive and negative predictive values were calculated using a 2 × 2 table, with a 95% confidence interval. RESULTS: A total of 39 patients were included in the study. 14 PET studies were deemed positive and 25 PET studies were deemed negative; 12 true positives and 23 true negatives were found. This yielded a sensitivity of 92.9% (95% CI, 66.1-99.8), specificity of 92% (95% CI, 74-99), PPV of 86.7% (95% CI, 63.1-96.1), and NPV of 95.8% (95% CI, 79.1-98.4). CONCLUSIONS: The [11C]DTBZ PET has an excellent accuracy for differentiating idiopathic PD from other disorders.

[Breve recorrido histórico de la enfermedad de Parkinson a 200 años de su descripción].

The original description of what currently is known as Parkinson's disease was published 200 years ago. During both these centuries, knowledge on symptomatology, pathophysiology, genetics and pharmaceutical and surgical treatment has significantly increased; however, this nosological entity continues to be of imprecise origin and progressive evolution. In the present review, the historical events that contributed to describe and improve the understanding of this disease are summarized.

La descripción original de lo que ahora conocemos como enfermedad de Parkinson fue publicada hace 200 años. Durante estos dos siglos, el conocimiento sobre la sintomatología, fisiopatología, genética, tratamiento farmacológico y quirúrgico se ha incrementado notablemente; no obstante, esta entidad nosológica continúa siendo de origen impreciso y de curso progresivo. En la presente revisión se resumen los acontecimientos históricos que contribuyeron a describir y mejorar el entendimiento de esta enfermedad.

Two-hundred Years Later: Is Parkinson's Disease a Single Defined Entity?

An Essay on the Shaking Palsy, by James Parkinson, was published in 1817. Later, Jean-Martin Charcot better described some of the motor features of the disease and named the condition as "La Maladie de Parkinson." As understanding about the disease progressed, aided by both clinical expertise and technological developments, the definition of what is Parkinson's disease has evolved. Motor phenotype, non-motor symptoms, monogenic mutations, genetic risk factors, disease subtyping, and data-driven clusters, among other concepts, have given rise to the hypothesis that Parkinson's disease may be not one well-defined entity but several different diseases encompassed as a levodopa-responsive Parkinsonism. This review present and discusses several of these factors and how they may support or not the notion of Parkinson's being one or more diseases. In summary, current evidence appears to be insufficient at this moment to clarify this issue. Parkinson's disease will continue to be an evolving concept over the years to come.

Impact of a Movement Disorders Clinic on the trends of Parkinson's Disease Consultations at a Tertiary Referral Center.

BACKGROUND: Outpatient clinics for movement disorders provide specialized diagnosis and treatment services for the specific needs of this patient population. OBJECTIVE: Describe the impact of implementing a Movement Disorder Clinic on the trends of consultations per year and hospitalizations of subjects with Parkinson's disease at a tertiary referral center. METHODS: A retrospective study was carried out. We collected data from the Clinical File Archive and the Epidemiology Department at the National Institute of Neurology and Neurosurgery in Mexico. Data from January 1, 1999 through December 31, 2015 were included for analysis. RESULTS: The number of total consultations had an increase of 632.1% between 1999 and 2015. Follow-up visits represented up to 95% of the consultations. Peaks found correlated with the inclusion of new specialists in the clinic. Regarding hospitalization, the number of patients discharged with a diagnosis of Parkinson's disease increased from a median of 17 (range 9-35) to 46 patients (range 31-53) per year. CONCLUSIONS: The implementation of a multidisciplinary Movement Disorders Outpatient Clinic in a tertiary referral center had a direct impact on the total number of consultations per year, mainly follow-up visits. The latter may reflect in an improvement in the quality of care.

[Prevalence of neuropsychiatric disorders in drug-naive subjects with Parkinson's disease (PD)]. / Prevalencia de trastornos neuropsiquiátricos en pacientes con enfermedad de Parkinson (EP) no tratados.

INTRODUCTION: Parkinson's disease is characterized by a broad spectrum of neuropsychiatric manifestations. Its pathophysiology has been associated with the disease itself as well as with the dopaminergic treatment. MATERIAL AND METHODS: A cross-sectional study was conducted in drug-naive patients with early Parkinson's disease. All participants were evaluated through a set of scales for specific neuropsychiatric symptoms including: cognition, depression, anxiety, apathy, psychosis, and impulse control disorder. RESULTS: A total of 63 patients with Parkinson were included, of whom 26 (41.3%) subjects had some degree of cognitive impairment; seven (11.1%) had depression and 11 (15.8%) subjects had anxiety. Regarding the other symptoms, a total of 12 (19%) patients showed apathy, seven (11.1%) had psychosis, and eight (12.6%) patients had symptoms related to impulse control disorders. CONCLUSION: Neuropsychiatric disorders are common in drug-naive patients with early Parkinson's disease. Given the impact of these symptoms on quality of life, identification and proper treatment is essential.

Proton Magnetic Resonance Spectroscopy Changes in Parkinson's Disease With and Without Psychosis.

BACKGROUND: Psychosis prevalence in Parkinson's disease is estimated at 8-30%. Proton magnetic resonance spectroscopy measures specific metabolites as markers of cell functioning. OBJECTIVE: To study N-acetyl-aspartate and glutamate levels in the caudate and putamen nuclei in subjects with Parkinson's disease with and without psychosis. METHODS: We included 20 non-demented Parkinson's disease patients with psychosis and 20 Parkinson's disease patients without psychosis matched for age, sex, disease duration, and levodopa equivalent daily dose, all attended at an academic medical center. Proton magnetic resonance spectroscopy scans were performed in a 3T GE whole-body scanner. RESULTS: Decreased glutamate levels scaled to creatine were found in the dorsal caudate (p = 0.005) and putamen (p = 0.007) of the Parkinson's disease psychosis group compared with the without psychosis group. Glutamate plus glutamine levels scaled to creatine and N-acetyl-aspartate levels scaled to creatine were also significantly reduced in the dorsal caudate of the Parkinson's disease with psychosis group (p = 0.018 and p = 0.011, respectively). No group differences were found for any of the other metabolites in the two regions of interest. CONCLUSIONS: Our findings suggest that decreased metabolite levels in specific brain areas may be implicated in the development of psychosis in Parkinson's disease.

[Prevalence, associated factors and phenomenology of psychosis in patients with Parkinson's disease]. / Prevalencia, factores asociados y fenomenología de la psicosis en pacientes con enfermedad de Parkinson.

INTRODUCTION: Psychosis associated with Parkinson's disease is a major neuropsychiatric complication; it has been reported that 60% of patients will develop psychosis during the disease evolution. Its pathophysiology is multifactorial and clinically psychotic phenomena include minor hallucinations and confusional states. MATERIAL AND METHODS: We performed a cross-sectional study in patients with Parkinson's disease from a tertiary hospital using a thoughtful neurological and neuropsychiatric evaluation along with specific scales for non-motor symptoms, depression, cognition, and presence and severity of psychotic symptoms and hallucinations. RESULTS: We included a total of 236 patients with Parkinson's disease, of which 33 (13.9%) patients met the criteria for psychosis at the time of the evaluation. Visual hallucinations were the most common symptom. Age (p = 0.004), age at onset of the disease (p = 0.007) and its duration (p = 0.004), use of levodopa (p = 0.02), and use of amantadine (p = 0.004) were the main factors associated with the presence of psychosis. CONCLUSION: Psychosis in Parkinson's disease is a relatively common manifestation and is mainly associated with clinical and demographic factors. Early recognition will optimize management and improve the quality of life of patients and their caregivers.