Effects of gabapentin enacarbil on restless legs syndrome and leg pain in dementia with Lewy bodies

Restless legs syndrome (RLS) is a common neurological disorder. Dementia with Lewy bodies (DLB) is the second most common form of neurodegenerative dementia after Alzheimer's disease. Both RLS and DLB can be effectively treated by dopaminergic medications, suggesting the role of dopamine dysfunction in the pathogenesis of both diseases. Here, I report on a Japanese woman with probable DLB and RLS who was treated with gabapentin enacarbil, a non‐dopaminergic agent. Because a dopamine agonist, a first‐line therapy for moderate to severe RLS, caused the occurrence of metamorphopsia, an alternative treatment of gabapentin enacarbil was used; this treatment improved the patient's RLS without worsening her psychiatric symptoms. An alternative treatment is desirable for DLB patients with RLS because they often experience intolerable side‐effects with a dopamine agonist, especially visual hallucinations. Administering gabapentin enacarbil also improved the continuous leg pain that occurred in conjunction with the development of RLS. Although the neurobiological mechanism in the development of pain remains unclear, a range of non‐dopaminergic structures likely mediated pain processing in DLB in the present case based on neuropharmacological results. This is the first report reporting the effects of gabapentin enacarbil for RLS and leg pain in a DLB patient with psychiatric symptoms.     

Clinical milestones in Parkinson's disease: A 7-year population-based incident cohort study

IntroductionClinical staging of Parkinson's disease (PD) is important for patient management and prognosis. The non-motor and functional features visual hallucinations, recurrent falls, dementia and nursing home placement are currently not included in clinical staging schemes, but have been suggested as clinical milestones with important prognostic implications in advanced PD. In this study, we sought to evaluate the potential of these four milestone events for clinical staging and prognosis during the early years of the disease.MethodsWe recruited 185 patients with incident PD and monitored prospectively every six months through seven years for emergence and consequences of four clinical milestones.ResultsOne or more milestones were reached in 53.0%. Of the patients who reached the milestones, visual hallucinations appeared after a median of 3.3 (interquartile range 1.3–4.9) years from diagnosis, recurrent falls after 3.8 (2.8–5.2) years, dementia after 4.0 (2.1–4.8) years and nursing home placement after 5.4 (3.9–6.7) years. Presence of any milestone was associated with occurrence of other milestones (relative risks 1.9–6.3; all p ≤ 0.001). Experiencing two or more milestones increased the risk of death during the study (relative risk 2.7, p = 0.03).ConclusionsIn early PD, visual hallucinations, recurrent falls, dementia and nursing home placement appear closely interrelated, possibly reflecting a shared neuropathological disease stage. All events convey important and sinister information on PD status and prognosis and are relatively easily accessible during routine clinical consultations. Therefore, they appear highly useful as clinical PD milestones and could possibly be incorporated into a novel disease rating scale.     

基于河南省致瘾致幻预警平台的药物致瘾致幻风险及成果分析

目的： 探索河南省医疗机构潜在致瘾致幻药品滥用预警平台的临床应用。方法： 通过河南省医疗机构潜在致瘾致幻药品滥用预警平台建立郑州大学第二附属医院潜在致瘾致幻药物滥用的主动监测和回顾性分析监测模式，收集潜在致瘾致幻药物滥用信息，以报告比值比法（ROR）法挖掘药物致瘾致幻风险，以ROR法的95% CI值判断预警信号的生成，分析药物滥用区域性流行特征，及时发现易造成致瘾致幻的药物。结果： 抽检2019年1月1日至2020年6月30日共计一年半的病例信息，涉及麻醉药品、苯二氮类镇静催眠药以及H₂受体拮抗剂等有效数据药品13个，其中有8种药品，10个品规药物ROR的95% CI>1，即10个品规药物有致瘾致幻事件的发生，注射用剂型药品致瘾致幻发生的风险高于口服制剂。结论： 通过对河南省平台的监测，对使用量大且集中使用的药物起到了很好的滥用监测效果，并进一步挖掘潜在用药风险信号，提前进行预警干预，降低药害事件的发生几率。     

Affectively Salient Meaning in Random Noise: A Task Sensitive to Psychosis Liability

Stable differences in the tendency to attribute meaning and emotional value to experience may represent an indicator of liability to psychosis. A brief task was developed assessing variation in detecting affectively meaningful speech (speech illusion) in neutral random signals (white noise) and the degree to which this was associated with psychometric and familial vulnerability for psychosis. Thirty patients, 28 of their siblings, and 307 controls participated. The rate of speech illusion was compared between cases and controls. In controls, the association between speech illusion and interview-based positive schizotypy was assessed. The hypothesis of a dose-response increase in rate of speech illusion across increasing levels of familial vulnerability for psychosis (controls, siblings of patients, and patients) was examined. Patients were more likely to display speech illusions than controls (odds ratio [OR] = 4.0, 95% confidence interval [CI] = 1.4–11.7), also after controlling for neurocognitive variables (OR = 3.8, 95% CI = 1.04–14.1). The case-control difference was more accentuated for speech illusion perceived as affectively salient (positively or negatively appraised) than for neutrally appraised speech illusions. Speech illusion in the controls was strongly associated with positive schizotypy but not with negative schizotypy. In addition, the rate of speech illusion increased with increasing level of familial risk for psychotic disorder. The data suggest that the white noise task may be sensitive to psychometric and familial vulnerability for psychosis associated with alterations in top-down processing and/or salience attribution.     

Hypermetabolism in the left thalamus and right inferior temporal area on positron emission tomography-statistical parametric mapping (PET-SPM) in a patient with Charles Bonnet syndrome resolving after treatment with valproic acid

Charles Bonnet syndrome (CBS) is characterized by the occurrence of complex visual hallucinations in visually impaired patients who understand that what they see is unreal. The pathophysiologic mechanism of CBS is poorly understood. However, hypermetabolism of the thalamocortical pathway as a result of deafferentation was recently proposed as a possible mechanism. A 69-year-old patient with CBS presented with a 5-year history of visual hallucinations after bilateral visual impairment, which had progressed to troublesome images of many unreal people and animals. Positron emission tomography-statistical parametric mapping (PET-SPM) imaging studies initially revealed hypermetabolism in the right inferior temporal area and left thalamus, which disappeared after treatment with valproic acid. This case, using PET-SPM analysis, supports the thalamic hypermetabolism theory of CBS.     

Characterization of diplopia in non-demented patients with Parkinson's disease

IntroductionAlthough diplopia is considered a frequent symptom of Parkinson's disease (PD), little is known about its clinical manifestation, associated mechanisms and treatment. Here we characterized binocular diplopia in non-demented PD patients in an interdisciplinary setting.MethodsPD patients were prospectively screened for diplopia, visual hallucinations, problems with spatial perception, contrast sensitivity, presence of blurred vision, and history of ophthalmological comorbidities via interview. Two groups of PD patients, one with and one without diplopia, underwent clinical and ophthalmological assessment to characterize diplopia in these patients. Clinical features were investigated using the Unified Parkinson's Disease Rating Scale and the Non-Motor Symptoms Scale.ResultsThe frequency of binocular diplopia was 29.6% (n = 37) in our cohort of 125 Parkinson's disease patients. Related mechanisms were heterogeneous including convergence insufficiency, strabismus, and motor fluctuations, as well as symptoms related to visual hallucinations. Diplopia was associated with other visual disturbances like visual hallucinations, blurred vision and problems with spatial perception. Beyond that, diplopia was found to be a predictive factor (3.2, odds ratio) for the occurrence of visual hallucinations in PD.ConclusionBinocular diplopia represents a frequent and relevant symptom in PD patients. Different subtypes should be considered due to different associated mechanisms including ophthalmic pathology and motor fluctuation, as well as intermediate to higher level visual processes. Diplopia seems to be part of a continuous spectrum of positive visual symptoms in Parkinson's disease.     

Cognitive triggers of auditory hallucinations: An experimental investigation

It has proved difficult to establish the internal process by which mental events are transformed into auditory hallucinations. The earlier stages of the generation of hallucinations may prove more accessible to research. Cognitions have been reported by patients as a trigger of auditory hallucinations, but the role of these preceding thoughts has not been causally determined. Therefore, the role of cognition in triggering auditory hallucinations was tested in an experimental study. Thirty individuals who experienced auditory hallucinations in social situations entered a neutral social situation presented using virtual reality. Participants randomised to the experimental condition were instructed to think their hallucination-preceding thoughts, and those randomised to the control condition were instructed to think neutral thoughts. Twenty-seven participants (93%) were able to spontaneously identify a cognition which preceded a hallucination. There was no difference between the experimental and control groups in the occurrence or severity of auditory hallucinations in virtual reality. Virtual reality did not lead to physical side effects or an increase in anxiety. The relationship between antecedent cognitions and auditory hallucinations is likely to be more complex than the one tested. It is argued that the effect of cognition on auditory hallucinations may be mediated by affect but this needs to be investigated through further experimental research.     

大剂量黄芪注射液治疗难治性心衰的临床观察

目的 :大剂量黄芪注射液治疗难治性心力衰竭。方法 :对 59例患者随机分为两组进行治疗。治疗组 3 0例 ,对照组 2 9例。结果 :两组显效率和总有效率比较均有非常显著性差异 (P<0 .0 1) 。结论 :加用大剂量黄芪注射液治疗难治性心衰有较满意的疗效。     

中西医结合治疗儿童慢性难治性哮喘初探

对小儿慢性难治性哮喘的中西医结合治疗进行探讨,并体会到中西医结合治疗效果较好;活血化瘀是治疗慢性难治性哮喘必不可少的治法;经常审慎而大胆地使用葶苈子,可提高疗效,未发现任何不良反应。     

难治性癫痫的外科治疗分析

目的总结难治性癫痫的临床特点,探索外科治疗该类疾病的临床经验。方法77例难治性癫痫患者中一侧半球大骨瓣开颅处理致痫灶21例;致痫主灶侧半球开颅联合胼胝体切开术29例;择期分阶段行双侧半球致痫灶手术27例。有54例次选择2种术式联合,44例次选择3种术式联合,10例次选择单纯低功率电凝热灼术。手术均在皮层脑电图(ECoG)监测下完成。手术后癫痫控制情况按Engel标准评判。结果随访时间7~76个月,平均37个月。Ⅰ级32例,Ⅱ级19例,Ⅲ级16例,Ⅳ10例。神经心理功能改善27例。术后18例出现并发症。随访期间15例症状消失,3例仍留有部分功能障碍。结论外科治疗难治性癫痫是一种有效的方法,它不仅可控制或减轻癫痫发作,还可改善患者的神经心理功能状态。