Parkinson's disease (PD) is a progressive neurological condition. Levodopa (LD) is the gold standard therapy for PD patients. Most PD patients in low-income areas cannot afford long-term daily ...Levodopa therapy. The aim of our study was to investigate if Mucuna pruriens (MP), a legume with high LD content that grows in tropical regions worldwide, might be potential alternative for poor PD patients.
We analyzed 25 samples of MP from Africa, Latin America and Asia. We measured the content in LD in various MP preparations (dried, roasted, boiled). LD pharmacokinetics and motor response were recorded in four PD patients, comparing MP vs. LD+Dopa-Decarboxylase Inhibitor (DDCI) formulations.
Median LD concentration in dried MP seeds was 5.29%; similar results were obtained in roasted powder samples (5.3%), while boiling reduced LD content up to 70%. Compared to LD+DDCI, MP extract at similar LD dose provided less clinical benefit, with a 3.5-fold lower median AUC.
Considering the lack of a DDCI, MP therapy may provide clinical benefit only when content of LD is at least 3.5-fold the standard LD+DDCI. If long-term MP proves to be safe and effective in controlled clinical trials, it may be a sustainable alternative therapy for PD in low-income countries.
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•Thousands of PD patients in low-income countries cannot afford Levodopa therapy.•Mucuna pruriens is a source of Levodopa, growing in all tropical areas worldwide.•Median Levodopa concentration in dried Mucuna pruriens seeds is about 5%.•Boiling reduces Levodopa content up to 70%, while roasting does not.•Clinical benefit if Levodopa dose is >3.5-fold standard Levodopa+DDCI formulations
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Freezing of gait (FOG) is a sudden episodic inability to produce effective stepping despite the intention to walk. It typically occurs during gait initiation (GI) or modulation and may lead to falls. ...We studied the anticipatory postural adjustments (imbalance, unloading, and stepping phase) at GI in 23 patients with Parkinson’s disease (PD) and FOG (PDF), 20 patients with PD and no previous history of FOG (PDNF), and 23 healthy controls (HCs). Patients performed the task when off dopaminergic medications. The center of pressure (CoP) displacement and velocity during imbalance showed significant impairment in both PDNF and PDF, more prominent in the latter patients. Several measurements were specifically impaired in PDF patients, especially the CoP displacement along the anteroposterior axis during unloading. The pattern of segmental center of mass (SCoM) movements did not show differences between groups. The standing postural profile preceding GI did not correlate with outcome measurements. We have shown impaired motor programming at GI in Parkinsonian patients. The more prominent deterioration of unloading in PDF patients might suggest impaired processing and integration of somatosensory information subserving GI. The unaltered temporal movement sequencing of SCoM might indicate some compensatory cerebellar mechanisms triggering time-locked models of body mechanics in PD.
Objective: To survey the safety of MRI in PD patients implanted with DBS devices. Background: MRI in patients with DBS implants is useful to confirm electrode placement, optimize programming and ...investigating complications. However, several medical centers do not perform MRI studies in DBS patients because of safety concerns. The safety profile of MRI in DBS patients has not been documented in large clinical series. Methods: 42 NPF Centers of Excellence (COEs) were asked to complete a questionnaire on MRI use and DBS. Results: Investigators from 40 of 42 (95%) NPF COEs completed the survey and 23 (58%) reported that they were currently performing brain MRI in DBS patients, while 3 (7.5%) had done it in the past. The 17 COEs currently not performing post-operative MRI for DBS listed the following reasons: 1) industry guidelines and/or warnings (53%); 2) decision deferred to outside department (29%); 3) liability/risk/safety (18%); 4) no active DBS program (18%); 5) no available MRI (12%); and 6) insurance and reimbursement concerns (6%). A total of 3304 PD patients with one or more DBS leads had a brain MRI scan, and 177 DBS patients had MRI of other body regions. In one case MRI was associated with an IPG failure without neurological sequelae after IPG replacement. No other complications were reported. Conclusions: these data provide evidence for a favorable risk/benefit ratio for brain MRI in patients with DBS implants. Further studies will need to address whether a re-assessment of more restrictive recommendations (i.e. very low SAR values) may be warranted.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
A brain-machine interface represents a promising therapeutic avenue for the treatment of many neurologic conditions. Deep brain stimulation (DBS) is an invasive, neuro-modulatory tool that can ...improve different neurologic disorders by delivering electric stimulation to selected brain areas. DBS is particularly successful in advanced Parkinson's disease (PD), where it allows sustained improvement of motor symptoms. However, this approach is still poorly standardized, with variable clinical outcomes. To achieve an optimal therapeutic effect, novel adaptive DBS (aDBS) systems are being developed. These devices operate by adapting stimulation parameters in response to an input signal that can represent symptoms, motor activity, or other behavioral features. Emerging evidence suggests greater efficacy with fewer adverse effects during aDBS compared with conventional DBS. We address this topic by discussing the basics principles of aDBS, reviewing current evidence, and tackling the many challenges posed by aDBS for PD.
Aim
To describe a new clinical tool, the Rett Syndrome Motor Evaluation Scale (RESMES) and to assess (loco‐)motor function in people with Rett syndrome (RTT).
Method
Formal assessment provided by ...physicians was followed by parents’ direct observation at home using the RESMES. Sixty females (mean SD age 12y 5mo 8y 9mo, range 3–40y) with a clinical diagnosis and genetically determined RTT participated in the study. Spearman's/Pearson's coefficients assessed the correlation between the clinicians’ and caregivers’ evaluations, as well as the correlation of RESMES scores with other scales, namely the Pain Assessment in Advanced Dementia, the Rett Assessment Rating Scale, the Modified Ashworth Scale, and hand function (assessed with a scale of evaluation of purposeful hand function). Scores provided by parents and clinicians were tested statistically by Mann–Whitney U test.
Results
Approximately 88% of patients had moderate to severe RTT symptoms and, on average, moderate motor impairment based on the RESMES. RESMES total scores provided by clinicians and caregivers were highly correlated (r=0.91), as were the subscale scores. Postural transition was a critical area of the RESMES, where parents systematically provided lower scores than clinicians, indicating milder degrees of disability. Severity of scoliosis and mutation type emerged as significant predictors of motor function.
Interpretation
The RESMES characterized the (loco‐)motor impairments of the patients with RTT well. It also showed a close correlation between the evaluations of clinicians and caregivers, with the possible exception of postural transition tasks, which should be carefully addressed in a clinical setting. The type of mutation and presence of scoliosis should be evaluated, as they predicted the ability to walk.
What this paper adds
Caregivers at home can reliably assess motor function in Rett syndrome using the Rett Syndrome Motor Evaluation Scale (RESMES).
RESMES scores provided by clinicians and parents were highly correlated.
The severity of scoliosis and the genetic mutation predicted standing and walking abilities.
Resumen
Función motora en el síndrome de Rett: comparación de evaluaciones clínicas y parentales
Objetivo
Describir una nueva herramienta clínica, la Escala de Evaluación Motora del Síndrome de Rett (RESMES) y evaluar la función motora (locomotora) en personas con síndrome. de Rett (RTT).
Metodo
La evaluación formal proporcionada por los médicos fue seguida por la observación directa de los padres en el hogar utilizando los RESMES. Sesenta mujeres (edad media 12 años 5 mesesDS =8 años 9 meses, rango 3‐40 años) con diagnóstico clínico y genético de RTT participaron en el estudio. Los coeficientes de Spearman / Pearson evaluaron la correlación entre las evaluaciones de los médicos y los cuidadores, así como la correlación de las puntuaciones de RESMES con otras escalas, como la Evaluación del Dolor en la Demencia Avanzada (Pain Assessment in Advanced Dementia), la Escala de Calificación de la Evaluación de Rett (Rett Assessment Rating Scale), la Escala de Ashworth modificada y la función de la mano (evaluado con una escala de evaluación de la función voluntaria de la mano). Las puntuaciones proporcionadas por los padres y los clínicos se evaluaron estadísticamente mediante la prueba U de Mann‐Whitney.
Resultados
Aproximadamente el 88% de los pacientes tenían síntomas de RTT de moderados a severos y, en promedio, una discapacidad motora moderada basada en los puntajes de RESMES. Se encontró una correlación muy alta (r = 0,91) entre los puntajes totales de RESMES proporcionados por los médicos y cuidadores, al igual que los puntajes con las otras escalas. La transición postural fue un área crítica de RESMES, donde los padres proporcionaron sistemáticamente puntuaciones más bajas que los clínicos, lo que indica grados más leves de discapacidad. La gravedad de la escoliosis y el tipo de mutación fueron factores significativamente predictivos de la función motora.
Interpretación
Los puntajes de RESMES caracterizaron bien las alteraciones motoras de las pacientes con RTT. Se encontró una estrecha correlación entre las evaluaciones de los médicos y los cuidadores, con la posible excepción de los cambios postural, que deben evaluarse con cuidado en un entorno clínico. Se debe considerar el tipo de mutación y la presencia de escoliosis, ya que predijeron la capacidad de caminar.
Função motora na síndrome de Rett: comparando avaliações clínicas e dos pais
Objetivo
Descrever uma nova ferramenta clínica, a Escala de avaliação motora da síndrome de Rett (RESMES) e avaliar a função (loco)motora em pessoas com síndrome de Rett (RTT).
Método
A avaliação formal por médicos foi seguida por observação direta dos pais em casa usando a RESMES. Sessenta meninas (média DP idade 12a 5m 8a 9m, variação 3–40a) com diagnóstico clínico e RTT determinada geneticamente participaram no estudo. Coeficientes de Spearman/Pearson avaliaram a correlação entre avaliações dos clínicos e cuidadores, assim como as correlações dos escores na RESMES com outras escalas: Avaliação da Dor na Demência avançada (Pain Assessment in Advanced Dementia), Escala de Classificação de Rett (Rett Assessment Rating Scale), a Escala de Ashworth Modificada, e função manual (avaliada com uma escala de avaliação da função manual voluntária). Os escores fornecidos pelos pais e clínicos foram testados estatisticamente com o teste de Mann–Whitney U.
Resultados
Aproximadamente 88% dos pacientes tinham sintomas de RTT de moderados a severos e, em média, comprometimento motor moderado na RESMES. Os escores totais da RESMES dados pelos clínicos e cuidadores foram altamente correlacionados (r=0,91), assim como os escores das subescalas. Transição postural foi uma área crítica da RESMES, em que pais sistematicamente ponturam mais baixo que os clínicos, indicando graus mais leves de incapacidade. A severidade da escoliose e tipo de mutação emergiram como preditores significativos da função motora.
Interpretação
A RESMES caracterizou bem as deficiências (loco) motoras de pacientes com RTT. Também mostrou correlação próxima entre as avaliações de clínicos e cuidadores, com a possível exceção das tarefas de transição postural, as quais devem ser cuidadosamente abordadas no contexto clínico. O tipo de mutação e presença de escoliose devem ser avaliados, pois predizem a capacidade de andar.
What this paper adds
Caregivers at home can reliably assess motor function in Rett syndrome using the Rett Syndrome Motor Evaluation Scale (RESMES).
RESMES scores provided by clinicians and parents were highly correlated.
The severity of scoliosis and the genetic mutation predicted standing and walking abilities.
This article is commented on by Lotan on page 864 of this issue.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Postural instability, in particular at gait initiation (GI), and resulting falls are a major determinant of poor quality of life in subjects with Parkinson's disease (PD). Still, the contribution of ...the basal ganglia and dopamine on the feedforward postural control associated with this motor task is poorly known. In addition, the influence of anthropometric measures (AM) and initial stance condition on GI has never been consistently assessed. The biomechanical resultants of anticipatory postural adjustments contributing to GI imbalance (IMB), unloading (UNL), and stepping phase) were studied in 26 unmedicated subjects with idiopathic PD and in 27 healthy subjects. A subset of 13 patients was analyzed under standardized medication conditions and the striatal dopaminergic innervation was studied in 22 patients using FP-CIT and SPECT. People with PD showed a significant reduction in center of pressure (CoP) displacement and velocity during the IMB phase, reduced first step length and velocity, and decreased velocity and acceleration of the center of mass (CoM) at toe off of the stance foot. All these measurements correlated with the dopaminergic innervation of the putamen and substantially improved with levodopa. These results were not influenced by anthropometric parameters or by the initial stance condition. In contrast, most of the measurements of the UNL phase were influenced by the foot placement and did not correlate with putaminal dopaminergic innervation. Our results suggest a significant role of dopamine and the putamen particularly in the elaboration of the IMB phase of anticipatory postural adjustments and in the execution of the first step. The basal ganglia circuitry may contribute to defining the optimal referent body configuration for a proper initiation of gait and possibly gait adaptation to the environment.
Objectives
There is growing evidence that Parkinson’s disease and diabetes are partially related diseases; however, the association between the two, and the impact of specific treatments, are still ...unclear. We evaluated the effect of T2D and antidiabetic treatment on age at PD onset and on all-cause mortality.
Research design and methods
The standardized rate of T2D was calculated for PD patients using the direct method and compared with subjects with essential tremor (ET) and the general Italian population. Age at onset and survival were also compared between patients without T2D (PD-noT2D), patients who developed T2D before PD onset (PD-preT2D) and patients who developed T2D after PD onset (PD-postT2D).
Results
We designed a retrospective and prospective study. The T2D standardized ratio of PD (
N
= 8380) and ET (
N
= 1032) patients was 3.8% and 6.1%, respectively, while in the Italian general population, the overall prevalence was 5.3%. In PD-preT2D patients, on antidiabetic treatment, the onset of PD was associated with a + 6.2 year delay (
p
< 0.001) while no difference was observed in PD-postT2D. Occurrence of T2D before PD onset negatively affected prognosis (adjusted hazard ratio = 1.64 95% CI 1.33–2.02;
p
< 0.001), while no effect on survival was found in PD-postT2D subjects (hazard ratio = 0.86, 95% CI 0.53–1.39;
p
= 0.54).
Conclusions
T2D, treated with any antidiabetic therapy before PD, is associated with a delay in its onset. Duration of diabetes increases mortality in PD-preT2D, but not in PD-postT2D. These findings prompt further studies on antidiabetic drugs as a potential disease-modifying therapy for PD.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•Dysfunctional gait initiation in progressive supranuclear palsy relates to poor feedforward motor control.•Hypometabolism of the caudate nucleus impairs programming of anticipatory postural ...adjustments.•Thalamic hypometabolism correlates with the center of mass kinematic resultants of anticipatory postural adjustments.
The initiation of gait is a highly challenging task for the balance control system, and can be used to investigate the neural control of upright posture maintenance during whole-body movement. Gait initiation is a centrally-mediated motion achieved in a principled, controlled manner, including predictive mechanisms (anticipatory postural adjustments, APA) that destabilize the antigravitary postural set of body segments for the execution of functionally-optimized stepping. Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by early impairment of balance and frequent falls. The neural correlates of postural imbalance and falls in PSP are largely unknown. We biomechanically assessed the APA at gait initiation (imbalance, unloading, and stepping phases) of 26 patients with PSP and 14 age-matched healthy controls. Fourteen of 26 enrolled patients were able to perform valid gait initiation trials. The influence of anthropometric and base-of-support measurements on the biomechanical outcome variables was assessed and removed. Biomechanical data were correlated with clinical findings and, in 11 patients, with brain metabolic abnormalities measured using positron emission tomography and 2-deoxy-2-18Ffluoro-D-glucose. Patients with PSP showed impaired modulation of the center of pressure displacement for a proper setting of the center of mass momentum and subsequent efficient stepping. Biomechanical measurements correlated with “Limb motor” and “Gait and midline” subscores of the Progressive Supranuclear Palsy Rating Scale. Decreased regional glucose uptake in the caudate nucleus correlated with impaired APA programming. Hypometabolism of the caudate nucleus, supplementary motor area, cingulate cortex, thalamus, and midbrain was associated with specific biomechanical resultants of APA. Our findings show that postural instability at gait initiation in patients with PSP correlates with deficient APA production, and is associated with multiple and distinctive dysfunctioning of different areas of the supraspinal locomotor network. Objective biomechanical measures can help to understand fall-related pathophysiological mechanisms and to better monitor disease progression and new interventions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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