Manejo de la enfermedad de Parkinson y otros trastornos del movimiento en mujeres en edad fértil: Parte 1

IntroductionThe main challenge of Parkinson's disease in women of childbearing age is managing symptoms and drugs during pregnancy and breastfeeding. The increase in the age at which women are having children makes it likely that these pregnancies will become more common in future.ObjectivesThis study aims to define the clinical characteristics of women of childbearing age with Parkinson's disease and the factors affecting their lives, and to establish a series of guidelines for managing pregnancy in these patients.ResultsThis consensus document was developed through an exhaustive literature search and a discussion of the available evidence by a group of movement disorder experts from the Spanish Society of Neurology.ConclusionsParkinson's disease affects all aspects of sexual and reproductive health in women of childbearing age. Pregnancy should be well planned to minimise teratogenic risk. A multidisciplinary approach should be adopted in the management of these patients in order to take all relevant considerations into account.     

Buried Bumper Syndrome: A common complication of levodopa intestinal infusion for Parkinson disease

BackgroundPercutaneous endoscopic gastrostomy (PEG) is required for Levodopa/Carbidopa Intestinal Gel (LCIG) delivery in patients with advanced Parkinson's disease (PD) as well as for enteral feeding in a variety of neurological disorders. Buried Bumper Syndrome (BBS) is a serious complication of PEG. The frequency of BBS in patients receiving LCIG treatment has never been reported.ObjectivesTo compare the frequency of BBS in patients on LCIG treatment or on enteral feeding over the past 12 years and identify possible risk factors.MethodsWe reviewed prospectively recorded data from 2009 to 2020 on two case-series: LCIG-treated PD patients and non-PD patients on enteral nutrition. We identified all BBS incidences. Patients’ characteristics, clinical manifestations, BBS management, possible risk factors and outcomes were analyzed.ResultsDuring the 12 years, 35 PD patients underwent PEG insertion for LCIG infusion, and 123 non-PD patients for nutritional support. There were eight cases of BBS in six PD patients (17.1%). Six of them were effectively managed without treatment discontinuation. Of the enteral feeding patients, only one developed BBS (0.8%) (p < 0.001). We identified inappropriate PEG site aftercare, weight gain, early onset PD, longer survival, treatment duration, dementia and PEG system design as potential risk factors for BBS development.ConclusionsBBS occurs more frequently in LCIG patients than in patients receiving enteral feeding. If detected early, it can be successfully managed, and serious sequalae or treatment discontinuation can be avoided. Regular endoscopic follow-up visits of LCIG-treated patients and increased awareness in patients and clinicians are recommended.     

Should we start integrating genetic data in decision-making on device-aided therapies in Parkinson disease? A point of view

Parkinson disease (PD) is a complex heterogeneous neurodegenerative disorder. Association studies have revealed numerous genetic risk loci and variants, and about 5–10% suffer from a monogenic form. Because the presentation and course of PD is unique to each patient, personalized symptomatic treatment should ideally be offered to treat the most disabling motor and non-motor symptoms. Indeed, clinical milestones and treatment complications that appear during disease progression are influenced by the genetic imprint. With recent advances in PD, more patients live longer to become eligible for device-aided therapies, such as apomorphine continuous subcutaneous infusion, levodopa duodenal gel infusion, and deep brain stimulation surgery, each with its own inclusion and exclusion criteria, advantages and disadvantages. Because genetic variants influence the expression of particular clinical profiles, factors for better or worse outcomes for device-aided therapies may then be proactively identified. For example, mutations in PRKN, LRRK2 and GBA express phenotypes that favor suitability for different device therapies, although with marked differences in the therapeutic window; whereas multiplications of SNCA express phenotypes that make them less desirable for device therapies.     

谷氨酸受体在左旋多巴诱导的异动症中的相关研究进展

在帕金森病(PD)患者中,长期使用左旋多巴而诱导的异动症(LID)显著影响着左旋多巴的疗效及患者的生活质量,现有的应对方案效果也均不甚理想,其原因与LID的机制目前尚未完全阐明密切相关。近年来越来越多的研究证实,谷氨酸能系统与多巴胺能系统紧密关联,谷氨酸受体在LID中的作用也日益凸显,特别是代谢型谷氨酸受体(mGluR)4、mGluR5以及部分离子型谷氨酸受体(iGluRs)在LID的机制研究和临床药物研究中更是关注热点。笔者现对各类谷氨酸受体在LID中的变化、作用以及相关的临床研究进展进行综述,以期为PD患者中LID的诊治和机制阐明提供新思路。     

Levodopa and neuropathy risk in patients with Parkinson disease: Effect of COMT inhibition

ObjectiveOur purpose was to determine whether the use of catechol-O-methyltransferase-inhibitors (ICOMT) can reduce the risk of developing levodopa (LD)-induced neuropathy in Parkinson's disease (PD) patients.MethodsA multicentre study of 197 PD patients was performed. 144 were exposed to LD for more than three years (LELD group); 53 simultaneously assumed Entacapone for at least eighteen months (LELD_ICOMT group).ResultsThe prevalence of neuropathy in LELD patients was 19.4% whereas it was 5.7% in LELD_ICOMT group with a significant difference (p = 0.025). In LELD_ICOMT cohort the daily LD dose and serum VB12 levels were significantly higher (p < 0.0001), the serum Hcy levels were significantly lower (p = 0.001) compared to LELD group.ConclusionOur results suggest that ICOMT could have a protective effect on the development of LD-induced neuropathy. Their action probably occurs through the metabolic rebalancing of the one-carbon-pathway cycle and is independent of the PD duration and severity and the duration of LD intake.     

Clinical patterns of gait freezing in Parkinson's disease and their response to interventions: An observer-blinded study

BackgroundFreezing of gait (FOG) in Parkinson's disease (PD) is provoked by specific situations. The sensitivity of these situations to detect FOG and the relative FOG response to l-dopa and subthalamic nucleus deep brain stimulation (STN-DBS) is unknown.MethodsTwo blinded reviewers analyzed the video recordings of a standardized patient assessment before and 10 months after DBS-implantation of 124 PD patients with positive FOG according to the Unified Parkinson Rating Scale part II item 14. Baseline evaluations were done under 2 conditions (OFF- and ON-drug states). Postoperatively, the patients were evaluated under 4 conditions (OFF-drug/OFF-stim, OFF-drug/ON-stim, ON-drug/OFF-stim, and ON-drug/ON-stim). FOG frequency and its severity was rated during different provoking situations (start, turning, reaching a destination and open space hesitations) during a standardized walking task. Cumulative link mixed models were calculated to investigate the immediate and carry-over effect of medication and stimulation.ResultsEighty-one percent of patients presented FOG at least in one provoking situation on video assessment. During turning, the FOG severity was significantly worse than for the other subtypes (p < 0.0001). Both interventions improve all FOG subtypes similarly. The effect size of l-dopa and STN-DBS on subtypes were similar (p > 0.05), but the combined intervention had a stronger effect on FOG severity (p < 0.0001) compared to each intervention separately. FOG severity was lower at follow-up OFF compared to baseline OFF condition (p < 0.02) demonstrating a carry-over effect of STN-DBS.ConclusionTurning is the most sensitive provoking situation for gait freezing. STN-DBS and l-dopa improve all FOG subtypes similarly, their effect is stronger in combination.     

GCH1基因突变致多巴反应性肌张力不全一例

多巴反应性肌张力不全（DRD）是一种常染色体显性或隐性遗传运动障碍疾病,病理特征为黑质纹状体多巴胺含量减少,主要表现为儿童期肌张力障碍, 小剂量左旋多巴可以改善症状。三磷酸鸟苷环化水解酶1（GCH1）基因是其致病基因之一。该文报道1例GCH1基因突变所致的DRD患儿,其以步态异常为主诉,行走时出现肌张力不全姿势,症状晨轻暮重,经基因检测证实其GCH1基因出现杂合性突变。接受小剂量左旋多巴治疗后患儿神经系统体征基本消失,于小儿神经科门诊随诊2年,运动功能良好。临床上对于病因不明的肌张力障碍患儿, 需警惕DRD的可能, 尽早识别和治疗可明显改善预后,预防残疾的发生。     

早期肠道菌群干预对帕金森病患者便秘症状及多巴丝肼疗效的影响

目的 探讨早期肠道菌群干预对帕金森病（PD）患者肠道便秘症状及多巴丝肼疗效的影响,为临床治疗提供参考。方法 纳入2015月1月至2017年10月我院神经内科初次诊断的PD患者114例,随机分为肠道菌群干预组（n=57）与对照组（n=57）,两组均予多巴丝肼片常规初始治疗,干预组在此基础上加用三联活菌制剂调理肠道菌群,采用便秘患者生活质量量表（PAC-QOL）等评估患者便秘症状及满意度,采用统一帕金森病评定量表（UPDRS-Ⅲ）等评估两组患者治疗前后的运动症状及心理状态。结果 1干预组较治疗前及较对照组的PAC-QOL,Bristol粪便性状量表（BSFS）评分改善显著,差异有统计学意义（P<0.05）;2两组患者较治疗前UPDRS-Ⅲ运动评分均有改善,差异有统计学意义（P<0.05）,干预组较对照组4周时UPDRS-Ⅲ评分有下降,差异有统计学意义（P<0.05）;3干预组较对照组治疗后医院焦虑量表（HAD-A）、医院抑郁量表（HAD-D）、匹兹堡睡眠质量指数（PSQI）评分均有下降,差异有统计学意义（P<0.05）。结论 早期肠道菌群干预能有效改善PD患者的便秘症状及焦虑睡眠等心理状态,可能有早期增强多巴丝肼制剂对运动症状的疗效,但远期影响仍有待研究。     

Dyskinesias and motor symptoms onset in Parkinson disease

PurposeTo assess, using a longitudinal follow-up study design, the relationship between the body site of motor symptoms onset and that of dyskinesias (LID) onset in 70 PD patients in whom LID were absent at the baseline but appeared at one of the follow-up visits; to investigate the demographic and clinical features associated with different sites of LID onset.MethodsMotor symptoms onset was retrospectively determined by asking patients which body part had first been affected by motor impairment. The site of LID onset was determined objectively in one of the follow-up visits.ResultsMotor symptoms started in the limbs in all patients (unilaterally in 91.4% and bilaterally in 8.6% of the patients). LID started unilaterally in the limbs in 25.8%, bilaterally in the limbs in 7.1%, in the cranio-cervical–axial region in 40% and in both the cranio-cervical–axial region and limbs in 27.1% of the patients. No significant association emerged between the site of motor symptoms onset and that of LID onset; a correlation did emerge between the site of motor symptoms onset and that of LID onset in patients with unilateral onset of both motor symptoms and LID. No differences were detected when the subgroups of patients with LID onset in different body regions were compared.ConclusionsThe partial association between the body site of motor symptoms and of LID onset likely reflects pathophysiological mechanisms underlying LID.     

18F-L-DOPA PET/CT显像诊断先天性高胰岛素血症的研究进展

先天性高胰岛素血症（CHI）是由于胰腺β细胞分泌过多的胰岛素导致顽固性的低血糖及与血糖水平不相称的相对高胰岛素血症。CHI的治疗方法包括内科治疗和外科手术治疗,对于内科治疗无效或效果不佳的患者常需要外科手术治疗。CHI主要分为局灶型和弥漫型,局灶型CHI可通过外科手术切除病灶而治愈,弥漫型CHI需进行胰腺次全切除术治疗。因此,手术治疗前明确病理类型至关重要。CT、MRI及超声等影像学检查对于鉴别局灶型与弥漫型CHI具有一定的局限性,而18F-左旋多巴PET/CT显像具有一定优势。笔者对18F-左旋多巴PET/CT显像诊断CHI进行了综述,对临床实践具有一定的指导意义。