A review of the neurotransmitter system associated with cognitive function of the cerebellum in Parkinson's disease

The dichotomized brain system is a concept that was generalized from the‘dual syndrome hypothesis’to explain the heterogeneity of cognitive impairment,in which anterior and posterior brain systems are independent but partially overlap.The dopaminergic system acts on the anterior brain and is responsible for executive function,working memory,and planning.In contrast,the cholinergic system acts on the posterior brain and is responsible for semantic fluency and visuospatial function.Evidence from dopaminergic/cholinergic imaging or functional neuroimaging has shed significant insight relating to the involvement of the cerebellum in the cognitive process of patients with Parkinson’s disease.Previous research has reported evidence that the cerebellum receives both dopaminergic and cholinergic projections.However,whether these two neurotransmitter systems are associated with cognitive function has yet to be fully elucidated.Furthermore,the precise role of the cerebellum in patients with Parkinson’s disease and cognitive impairment remains unclear.Therefore,in this review,we summarize the cerebellar dopaminergic and cholinergic projections and their relationships with cognition,as reported by previous studies,and investigated the role of the cerebellum in patients with Parkinson’s disease and cognitive impairment,as determined by functional neuroimaging.Our findings will help us to understand the role of the cerebellum in the mechanisms underlying cognitive impairment in Parkinson’s disease.

Retinal capillary plexus in Parkinson’s disease using optical coherence tomography angiography

AIM:To evaluate the alterations of the retinal microvasculature and foveal avascular zone in patients with Parkinson’s disease(PD)using optical coherence tomography angiography(OCT-A).METHODS:A retrospective study of PD patients examined in the Ophthalmology Department of the General Hospital of Athens,“Georgios Gennimatas”from March 2021 to March 2022 was conducted.Totally 44 patients with PD were included and 18 healthy controls were examined,hence a total of 124 eyes were enrolled in the study.The foveal and parafoveal superficial and deep capillary plexus vascular density(fSCP-VD,fDCP-VD,pSCP-VD,pDCP-CD)and foveal avascular zone(FAZ)were quantified with OCTA.Optical coherence tomography(OCT)was used to measure macular thickness.Our statistical analysis was conducted by using a mixed effect linear regression model.RESULTS:After adjustment for age and gender,the mean parafoveal superficial capillary plexus vascular density(pSCP-VD)and mean parafoveal deep capillary plexus vascular density(pDCP-VD)were significantly decreased in individuals with PD(P<0.001 in both)by-2.35(95%CI-3.3,-1.45)and-7.5(95%CI-10.4,-4.6)respectively.fSCP-VD and fDCP-VD didn’t approach statistical significance.The FAZ area and perimeter were significantly decreased(P<0.001 in both)by-0.1 mm^(2)(95%CI-0.13,-0.07)and-0.49 mm^(2)(95%CI-0.66,-0.32)respectively.Circularity didn’t approach statistical significance.Central retinal thickness(CRT)was significantly decreased in individuals with PD(P<0.001)by-23.1μm(95%CI-30.2,-16)and temporal retinal thickness(TRT)was decreased(P=0.025)by-11μm(95%CI-22,-1.5)while nasal retinal thickness(NRT)only approached statistical significance(P=0.066).CONCLUSION:The mean pSCP-VD,pDCP-VD,CRT and TRT are significantly decreased and FAZ is altered in individuals with PD.These findings can be potentially used as biomarkers for the diagnosis and evaluation of early PD.

Bone cement implantation syndrome during hip replacement in a patient with pemphigus and Parkinson’s disease: A case report

BACKGROUND Bone cement implantation syndrome(BCIS)is characterized by hypotension,arrhythmia,diffuse pulmonary microvascular embolism,shock,cardiac arrest,any combination of these factors,or even death following bone cement implantation.CASE SUMMARY An 80-year-old patient with pemphigus and Parkinson’s disease underwent total hip replacement under spinal subarachnoid block and developed acute pulmonary embolism after bone cement implantation.The patient received mask mechanical ventilation with a continuous intravenous infusion of adrenaline(2μg/mL)at a rate of 30 mL/h.Subsequently,the symptoms of BCIS were markedly alleviated,and the infusion rate of adrenaline was gradually reduced until the infusion was completely stopped 45 min later.The patient was then transferred to the Department of Orthopedics,and anticoagulation therapy began at 12 h postoperatively.No other complications were observed.CONCLUSION This is a rare case of BCIS in a high-risk patient with pemphigus and Parkinson’s disease.

Antibody-based immunotherapies for Parkinsonian syndromes

What is the rationale for immunotherapies in Parkinsonian syndromes (PS)? PS are neurodegenerative diseases which are clinically characterized by a hypokinetic phenotype in combination with additional motor and non-motor symptoms. One major pathological hallmark of all PS consists of a non-physiological detrimental accumulation of protein aggregates which appear intracellularly in neurons and glial cells but also in the extracellular space (Wong and Krainc, 2017). Depending on the pathogenic protein, PS can be divided into synucleinopathies, characterized by aggregation of the protein alpha-Synuclein (aSyn), and tauopathies, characterized by aggregation of the protein Tau (Levin et al., 2016;Poewe et al., 2017). Clinical syndromes of synucleinopathies include Parkinson’s disease (PD), multiple system atrophy (MSA) and dementia with Lewy bodies, and tauopathies include progressive supranuclear palsy (PSP) and corticobasal degeneration.

Concomitant Othello syndrome and impulse control disorders in a patient with Parkinson’s disease:A case report

BACKGROUND Othello syndrome(OS)is characterized by delusional beliefs concerning the infidelity of a spouse or sexual partner,which may lead to extreme behaviors.Impulse control disorders refer to behaviors involving repetitive,excessive,and compulsive activities driven by an intense desire.Both OS and impulse control disorders in Parkinson’s disease(PD)may be side effects of dopamine agonists.At present,there are only a few case reports and studies related to PD with concomitant OS and impulse control disorders.CASE SUMMARY We describe a 70-year-old male patient with PD,OS,and impulse control disorders,who presented with a six-month history of the delusional belief that his wife was having an affair with someone.He began to show an obvious increase in libido presenting as frequent masturbation.He had been diagnosed with PD ten years earlier and had no past psychiatric history.In his fourth year of PD,he engaged in binge eating,which lasted approximately one year.Both OS and hypersexuality were alleviated substantially after a reduction of his pramipexole dosage and a prescription of quetiapine.CONCLUSION Given its potential for severe consequences,OS should be identified early,especially in patients undergoing treatment with dopamine agonists.

Ogilvie Syndrome Associated to Parkinson’s Disease

Ogilvie’s syndrome is an acute dilatation of a part or all of the colon and rectum without mechanical obstruction. The diagnosis is based on computed tomography (CT) that excludes organic or functional colonic obstruction and?ensures the detection of signs of severity. Rapid diagnosis leads to conservative measures and the resolution of obstruction. Delays in diagnosis can lead to complications imposing a surgical treatment and increased mortality rate. We report the case of a 52 years old woman with Parkinson’s disease, who presented Ogilvie’s syndrome. The initial assessment did not show signs of severity, so medical treatment was introduced but without improvement;for this reason, the surgical procedure was indicated as a cecostomy. There are several theories that explain the pathophysiology of Ogilvie’s syndrome;the most likely is the dysfunction of innervation of the colon which is due to Parkinson’s disease in our case. The diagnosis is based on computed tomography. The treatment is pharmacologic, conservative or surgical depending on the severity of the disease and its evolution.

The Tower of Hanoi for Evaluating Dysexecutive Syndrome in Patients with Parkinson’s:Standardization Values

Objective: The Tower of Hanoi measures executive functions using non-verbal content and requires perception of position in space. The main objective of this study is to standardize the use of the TOH as a measurement tool in Parkinson’s disease. Patients and Methods: Of the Control Group subjects, 192 (59.6%) were women, 223 subjects (69.25%) were able to perform the TOH with 3 discs. In the Parkinson’s Group, there were 57 women (39.3%), and 66 subjects (45.5%) did not get past that level. Results: If we take the TOH (with 3 or 4 discs) as a tool for discriminating between those who have dysexecutive syndrome and those who do not, we find that the Parkinson’s Group presents dysexecutive syndrome significantly more frequently than the Control Group (p ≤ 0.0064). Conclusion: We can conclude that dysexecutive syndrome is frequent in Parkinson’s patients and it is more prevalent than in the general population.

Effect of High Frequency Oscillatory Ventilation on EVLW and Lung Capillary Permeability of Piglets with Acute Respiratory Distress Syndrome Caused by Pulmonary and Extrapulmonary Insults

The effect of high frequency oscillatory ventilation（HFOV） at early stage on hemodynamic parameters, extravascular lung water（EVLW）, lung capillary permeability, CC16 and s ICAM-1 in piglets with pulmonary or extrapulmonary acute respiratory distress syndrome（ARDS） was explored. Central vein pressure（CVP） and pulse indicator continuous cardiac output（Pi CCO） were monitored in 12 anesthetized and intubated healthy piglets. Pulmonary ARDS（ARDSp） and extrapulmonary ARDS（ARDSexp） models were respectively established by lung lavage of saline solution and intravenous injection of oleic acid. Then the piglets received HFOV for 4 h. EVLW index（EVLWI）, EVLW/intratroracic blood volume（ITBV） and pulmonary vascular permeability index（PVPI） were measured before and after modeling（T0 and T1）, and T2（1 h）, T3（2 h）, T4（3 h） and T5（4 h） after HFOV. CC16 and s ICAM-1 were also detected at T1 and T5. Results showed at T1, T3, T4 and T5, EVLWI was increased more significantly in ARDSp group than in ARDSexp group（P〈0.05）. The EVLWI in ARDSp group was increased at T1（P=0.008）, and sustained continuously within 2 h（P=0.679, P=0.216）, but decreased at T4（P=0.007） and T5（P=0.037）. The EVLWI in ARDSexp group was also increased at T1（P=0.003）, but significantly decreased at T3（P=0.002） and T4（P=0.019）. PVPI was increased after modeling in both two groups（P=0.004, P=0.012）, but there was no significant change within 4 h（T5） under HFOV in ARDSp group, while PVPI showed the increasing trends at first, then decreased in ARDSexp group after HFOV. The changes of EVLW/ITBV were similar to those of PVPI. No significant differences were found in ΔEVLWI（P=0.13）, ΔPVPI（P=0.28） and ΔEVLW/ITBV between the two groups（P=0.63）. The significant decreases in both CC16 and s ICAM-1 were found in both two groups 4 h after HFOV, but there was no significant difference between the two groups. It was concluded that EVLWI and lung capillary permeability were markedly increased in ARDSp and ARDSexp groups. EVLW could be decreased 4 h after the HFOV treatment. HFOV, EVLW/ITBV and PVPI were increased slightly at first, and then decreased in ARDSexp group, while in ARDSp group no significant difference was found after modeling. No significant differences were found in the decreases in EVLW and lung capillary permeability 4 h after HFOV.

Intrastriatal Gene Transfer of Vascular Endothelial Growth Factor Rescues Dopaminergic Neurons in a Rat Parkinson's Disease Model

To examine the ability of intrastriatal gene transfer of vascular endothelial growth factor 165 mediated by adenoviral vector to rescue dopaminergic neurons in a rat model of Parkinson＇s disease （PD）, we constructed recombinant replication-deficent adenoviral vectors carrying the gene of VEGF165 （Ad-VEGF）, and injected Ad-VEGF （or Ad-LacZ and PBS as controls） into the striatum of rats 7 days after the lesion by 6-hydroxydopamine. The rat rotational behavior analysis and tyrosine hydroxylase （TH） immunohistochemistry were performed to assess the change of dopaminergic neurons. Our results showed that the rats receiving Ad-VEGF injection displayed a significant improvement in apomorphine-induced rotational behavior and a significant preservation of TH-positive neurons and fibers compared with control animals, It is concluded that intrastriatal gene transfer by Ad-VEGF may rescue the dopaminergic neurons from degeneration in a rat model of PD.

11C-β-CFT PET/CT与TCS检测对PD及APS的鉴别诊断价值研究

目的 探讨11C-甲基-N-2β-甲基酯-3β-(4-氟-苯基)托烷(11C-β-CFT)正电子发射断层显像/X线计算机体层成像(PET/CT)及经颅超声(TCS)检测对帕金森病(PD)及非典型帕金森综合征(APS)的鉴别诊断价值。方法 选取2020年5月至2021年6月该院核医学科行11C-β-CFT PET/CT检测的患者91例,其中PD 55例(PD组),APS 36例(APS组)。同时选取无相关神经系统疾病的健康者11例作为对照组。根据黑质回声强度将研究对象进一步分为阳性组(38例)和阴性组(41例)。比较各组相关检测参数,采用受试者工作曲线对相关指标诊断效能进行分析。结果 PD组、APS组、对照组11C-β-CFT PET/CT检测参数(尾状核不对称指数除外)比较,差异有统计学意义(P<0.05)。对照组各检测参数与PD组比较,差异有统计学意义(P<0.05)。PD组尾状核及前壳核11C-β-CFT摄取值与APS组比较,差异有统计学意义(P<0.05)。PD组、APS组、对照组黑质高回声面积分别为(0.12±0.19)、(0.22±0.17)、(0.23±0.23)cm2,差异无统计学意义(P>0.05)。阳性组、阴性组11C-β-CFT PET/CT检测参数比较,差异无统计学意义(P>0.05)。11C-β-CFT PET/CT检测参数与黑质高回声面积无相关性(P>0.05)。后壳核11C-β-CFT摄取值对PD和APS的诊断效能最佳。前壳核11C-β-CFT摄取值鉴别PD和APS的诊断效能相对较高,但仍不能对PD和APS准确鉴别。结论11C-β-CFT PET/CT检测有助于PD的诊断与鉴别诊断,对于存在运动症状的疑诊PD患者,TCS检测也可提供一些有效信息。

Frequency of Comorbid Musculoskeletal Problems in Patients with Parkinson’s Disease: What and When?

Background: Musculoskeletal problems, deteriorating posture and pain are common complaints/comorbidities in Parkinson’s disease (PD). The aim of this study was to investigate the frequency of comorbid musculoskeletal problems in PD, and their relationship with disease stage and severity. Methods: The study was approved by the local ethical committee of Duzce University numbered with 2018/52 on date 26.03.2018. Patients with PD (pwPD) underwent a detailed examination to investigate the possible comorbidity of musculoskeletal findings in the orthopedics and traumatology clinic. Socio-demographic features, disease characteristics, motor and non-motor scores were recorded. Results: Thirty-seven pwPD were enrolled in the study. Mean age was 68.75 ± 10.75 years. Comorbid musculoskeletal problems were rotator cuff syndrome (27%), knee osteoarthritis (24.3%), meniscus (13.5%), lumber disc herniation (10.8%), kyphosis (8.1%), myotendinous diseases (16.3%). Rotator-cuff disease and knee osteoarthritis were most common comorbidities, especially in the “mild” and “moderate” stages of pwPD. Conclusion: Since most of the pwPD, especially the ones that have musculoskeletal complaints prior to the diagnosis of PD, present to the orthopedics and traumatology clinics or physiotherapists, it is mandatory to enhance the awareness of the orthopedic surgeons, and physiotherapy specialist in order to keep PD in mind.

Collagen vascular disease-associated interstitial lung disease

Interstitial lung disease(ILD) is an important mani-festation of collagen vascular diseases. It is a common feature of scleroderma, and also occurs in dermatomyositis and polymyositis, mixed connective tissue disease, Sjogren's syndrome, rheumatoid arthritis, systemic lupus erythematosus, and Antineutrophil cytoplasmic antibody-associated vasculitis. When present, it is associated with increased morbidity and mortality, thus making early diagnosis important. In fact, in many patients, ILD may be the first manifestation of a collagen vascular disease. The most common symptoms are cough and dyspnea. The diagnosis is made based on pulmonary function tests showing restrictive lung disease and impaired oxygen diffusion and chest imaging showing ground glass infiltrates, interstitial thickening, and/or fibrosis. The most common histologic finding on lung biopsy is non-specific interstitial pneumonia, though organizing pneumonia and usual interstitial pneumonia may also be seen. Treatment is focused on addressing the underlying collagen vascular disease with immunosuppression, either with corticosteroids or a steroid-sparing agent such as cyclophosphamide, azathioprine, or mycophenolate, although the optimal agent and duration of therapy is not known. There are few clinical trials to guide therapy that focus specifically on the progression of ILD. The exception is in the case of scleroderma-associated ILD, where cyclophosphamide has been shown to be effective.

“XOS”综合反馈训练仪对帕金森氏综合征患者治疗效果的能量分析

采用能量分析法分析“XOS”综合运动训练反馈仪治疗帕金森氏综合征患者的效果,以进一步认识该仪器的治疗机制和作用。方法:8例年龄在27—73岁的帕金森氏综合征患者接受“XOS”训练至少1个月,训练前后进行综合力向量测试,并采用能量分析法分析训练前后的效果。结果:训练后的患者所做的正负功比值和正负功率比值接近正常人状况的人数增多,原来不能完成第三和第四区测试的人,经过训练后能完成整个区域的测试。结论:能量分析法可以证实帕金森氏综合征患者接受XOS训练后的效果。

脑多巴胺转运蛋白SPECT显像在鉴别帕金森病与血管性帕金森综合征中的价值

目的探讨脑99mTc-TRODAT-1多巴胺转运蛋白(DAT)SPECT显像对鉴别帕金森病(PD)和血管性帕金森综合征(VP)的临床应用价值。方法对30例PD组患者、24例VP组患者及16例健康对照(组)者分别进行99mTc-TRODAT-1 SPECT脑显像,剂量为740MBq。应用计算机感兴趣区技术及2个数学模型分别计算PD患者、VP患者及健康对照者双侧纹状体体积(V,cm3)、质量(W,g),代表相应部位DAT的功能水平。结果PD组双侧纹状体体积和质量均低于健康对照组及VP组,差异有统计学意义(P<0.01或P<0.05);PD患者症状对侧纹状体体积和质量均显著低于症状同侧(P<0.01)。VP组双侧纹状体体积和质量与健康对照组比较差异无统计学意义(P>0.05),其症状对侧与症状同侧纹状体体积和质量比较差异亦无统计学意义(P>0.05)。结论99mTc-TRODAT-1 DAT SPECT脑显像有助于PD与VP的鉴别诊断。

髓系细胞触发受体2在认知功能障碍中相关机制的研究进展

神经免疫系统对中枢神经系统的发育、衰老和损伤至关重要,逐渐成为人们研究的热点。髓系细胞触发受体2(TREM2)是免疫球蛋白超家族的一种跨膜受体,在中枢神经系统中主要表达于小胶质细胞。越来越多的研究表明,靶向TREM2对改善阿尔兹海默症、血管性痴呆、帕金森病、术后认知功能障碍、肥胖等疾病相关的认知功能障碍有很大的潜力。然而,其在认知功能障碍中的具体作用尚缺乏系统性的总结。故本文综述了TREM2在认知功能障碍中相关机制的最新研究进展,以期为认知功能障碍的治疗提供新的靶点。

黄煌辨体质分阶段治疗帕金森病经验

黄煌教授认为,“风胜则动”为帕金森病发生的基本病机,病位在肝与筋脉,与肺、脾、肾、心等脏关系密切。本病分为痰热生风证、热盛动风证、正虚风中证、阳虚动风证和虚劳化风证五个证型,并根据病程所处的不同阶段分期论治,以“方-病-人”诊疗模式辨其体质精准选方用药。早期以痰热生风证、热盛动风证为主,治宜清热,兼顾化痰、通腑、熄风、镇惊,方选柴胡加龙骨牡蛎汤、风引汤;中期以正虚风中证为主,治宜祛风散邪、益气养血并重,方选续命汤;晚期以阳虚动风证和虚劳化风证为主,治宜温补理虚,兼顾调气行水,方选真武汤、薯蓣丸。黄教授在临证施治过程中治风却不拘泥于熄风,求其生风之本、风中之因,切合病机,随证化裁,还注重调整体质偏颇,从整体上平衡阴阳、调畅气机、调和脏腑,辨体质分阶段治疗帕金森病,效如桴鼓。

多巴丝肼片联合盐酸普拉克索二联疗法对血管源性帕金森综合征患者GSH、CAT、T-SOD、UPDRS评分的影响

目的:研究多巴丝肼片联合盐酸普拉克索二联疗法对血管源性帕金森综合征(VP)患者谷胱甘肽(GSH)、过氧化氢酶(CAT)、总超氧化物歧化酶(T-SOD)以及帕金森综合评分量表(UPDRS)评分的影响。方法:将2018年3月-2020年3月铁岭市中心医院收治的91例VP患者纳入研究,将其以电脑随机数字表法分为二联组45例和常规组46例。常规组开展多巴丝肼片治疗,二联组则实施多巴丝肼片联合盐酸普拉克索治疗。分析两组临床疗效,治疗前后血清GSH、CAT、T-SOD水平,治疗前后UPDRS评分,以及不良反应发生情况。结果:二联组治疗总有效率高于常规组(P<0.05)。治疗后,二联组血清GSH、CAT、T-SOD水平均高于常规组(P<0.05)。治疗后,二联组各项UPDRS评分均低于常规组(P<0.05)。两组嗜睡、体位性低血压、视幻觉发生率比较,差异均无统计学意义(P>0.05)。结论:多巴丝肼片与盐酸普拉克索二联疗法治疗VP患者的临床效果显著,可明显改善机体氧化应激反应,减轻临床症状。

Imaging biomarkers in Parkinson’s disease and Parkinsonian syndromes:current and emerging concepts

Two centuries ago in 1817,James Parkinson provided the first medical description of Parkinson’s disease,later refined by Jean-Martin Charcot in the mid-to-late 19th century to include the atypical parkinsonian variants(also termed,Parkinson-plus syndromes).Today,Parkinson’s disease represents the second most common neurodegenerative disorder with an estimated global prevalence of over 10 million.Conversely,atypical parkinsonian syndromes encompass a group of relatively heterogeneous disorders that may share some clinical features with Parkinson’s disease,but are uncommon distinct clinicopathological diseases.Decades of scientific advancements have vastly improved our understanding of these disorders,including improvements in in vivo imaging for biomarker identification.Multimodal imaging for the visualization of structural and functional brain changes is especially important,as it allows a‘window’into the underlying pathophysiological abnormalities.In this article,we first present an overview of the cardinal clinical and neuropathological features of,1)synucleinopathies:Parkinson’s disease and other Lewy body spectrum disorders,as well as multiple system atrophy,and 2)tauopathies:progressive supranuclear palsy,and corticobasal degeneration.A comprehensive presentation of wellestablished and emerging imaging biomarkers for each disorder are then discussed.Biomarkers for the following imaging modalities are reviewed:1)structural magnetic resonance imaging(MRI)using T1,T2,and susceptibilityweighted sequences for volumetric and voxel-based morphometric analyses,as well as MRI derived visual signatures,2)diffusion tensor MRI for the assessment of white matter tract injury and microstructural integrity,3)proton magnetic resonance spectroscopy for quantifying proton-containing brain metabolites,4)single photon emission computed tomography for the evaluation of nigrostriatal integrity(as assessed by presynaptic dopamine transporters and postsynaptic dopamine D2 receptors),and cerebral perfusion,5)positron emission tomography for gauging nigrostriatal functions,glucose metabolism,amyloid and tau molecular imaging,as well as neuroinflammation,6)myocardial scintigraphy for dysautonomia,and 7)transcranial sonography for measuring substantia nigra and lentiform nucleus echogenicity.Imaging biomarkers,using the‘multimodal approach’,may aid in making early,accurate and objective diagnostic decisions,highlight neuroanatomical and pathophysiological mechanisms,as well as assist in evaluating disease progression and therapeutic responses to drugs in clinical trials.

Linking restless legs syndrome with Parkinson’s disease:clinical,imaging and genetic evidence

Restless legs syndrome(RLS)and Parkinson’s disease(PD)are both common neurological disorders.There has been much debate over whether an etiological link between these two diseases exists and whether they share a common pathophysiology.Evidence pointing towards a link includes response to dopaminergic agents in PD and RLS,suggestive of underlying dopamine dysfunction in both conditions.The extrastriatal dopaminergic system,in particular altered spinal dopaminergic modulation,may be variably involved in PD patients with RLS symptoms.In addition,there is now evidence that the nigrostriatal system,primarily involved in PD,is also affected in RLS.Furthermore,an association of RLS with the parkin mutation has been suggested.The prevalence of RLS has also been reported to be increased in other disorders of dopamine regulation.However,clinical association studies and functional imaging have produced mixed findings.Conflicting accounts of emergence of RLS and improvement in RLS symptoms after deep brain stimulation(DBS)also contribute to the uncertainty surrounding the issue.Among the strongest arguments against a common pathophysiology is the role of iron in RLS and PD.While elevated iron levels in the substantia nigra contribute to oxidative stress in PD,RLS is a disorder of relative iron deficiency,with symptoms responding to replacement therapy.Recent ultrasonography studies have suggested that,despite overlapping clinical features,the mechanisms underlying idiopathic RLS and RLS associated with PD may differ.In this review,we provide a concise summary of the clinical,imaging and genetic evidence exploring the link between RLS and PD.

Molecular imaging of movement disorders

Positron emission tomography measures the activity of radioactively labeled compounds which distribute and accumulate in central nervous system regions in proportion to their metabolic rate or blood flow. Specific circuits such as the dopaminergic nigrostriatal projection can be studied with ligands that bind to the pre-synaptic dopamine transporter or post-synaptic dopamine receptors(D1 and D2). Single photon emission computerized tomography(SPECT) measures the activity of similar tracers labeled with heavy radioactive species such as technetium and iodine. In essential tremor, there is cerebellar hypermetabolism and abnormal GABAergic function in premotor cortices, dentate nuclei and ventral thalami, without significant abnormalities in dopaminergic transmission. In Huntington's disease, there is hypometabolism in the striatum, frontal and temporal cortices. Disease progression is accompanied by reduction in striatal D1 and D2 binding that correlates with trinucleotide repeat length, disease duration and severity. In dystonia, there is hypermetabolism in the basal ganglia, supplementary motor areas and cerebellum at rest. Thalamic and cerebellar hypermetabolism is seen during dystonic movements, which can be modulated by globus pallidus deep brain stimulation(DBS). Additionally, GABA-A receptor activity is reduced in motor, premotor and somatosensory cortices. In Tourette's syndrome, there is hypermetabolism in premotor and sensorimotor cortices, as well as hypometabolism in the striatum, thalamus and limbic regions at rest. During tics, multiple areas related to cognitive, sensory and motor functions become hypermetabolic. Also, there is abnormal serotoninergic transmission in prefrontal cortices and bilateral thalami, as well as hyperactivity in the striatal dopaminergic system which can be modulated with thalamic DBS. In Parkinson's disease(PD), there is asymmetric progressive decline in striatal dopaminergic tracer accumulation, which follows a caudal-to-rostral direction. Uptake declines prior to symptom presentation and progresses from contralateral to the most symptomatic side to bilateral, correlating with symptom severity. In progressive supranuclear palsy(PSP) and multiple system atrophy(MSA), striatal activity is symmetrically and diffusely decreased. The caudal-to-rostral pattern is lost in PSP, but could be present in MSA. In corticobasal degeneration(CBD), there is asymmetric, diffuse reduction of striatal activity, contralateral to the most symptomatic side. Additionally, there is hypometabolism in contralateral parietooccipital and frontal cortices in PD; bilateral putamen and cerebellum in MSA; caudate, thalamus, midbrain, mesial frontal and prefrontal cortices in PSP; and contralateral cortices in CBD. Finally, cardiac sympathetic SPECT signal is decreased in PD. The capacity of molecular imaging to provide in vivo time courses of gene expression, protein synthesis, receptor and transporter binding, could facilitate the development and evaluation of novel medical, surgical and genetic therapies in movement disorders.