Overactive bladder in Parkinson's disease: alteration of brainstem raphe detected by transcranial sonography

Urinary dysfunction is very common in idiopathic Parkinson's disease (PD) and manifests primarily with symptoms of overactive bladder (OAB). Affection of central serotonergic systems has been suggested to play a role in OAB. The objective of this study was to evaluate whether in PD patients with OAB symptoms a specific alteration of the brainstem raphe (BR), which contains serotonergic neurons, can be detected with transcranial sonography (TCS). Of 116 PD patients enrolled, 19 had PD-related OAB symptoms (OAB+) unlike remaining 97 patients (OAB−). Patients were examined by a sonographer blinded to the clinical data. Reduced echogenicity of BR was found in 12 (63%) OAB+ patients but only in 18 (19%) of 93 assessable OAB− patients (Mann–Whitney U -test, P  < 0.001). In OAB+ patients, lower raphe echogenicity score was associated with longer duration of OAB symptoms ( anova , P  = 0.033). Other TCS findings such as echogenicity of substantia nigra, thalami, lenticular and caudate nuclei, and widths of third and lateral ventricles did not differ between OAB+ and OAB− patients. TCS findings suggest a pathogenetic role of BR in OAB related to PD. Alterations may reflect disturbance of its central serotonergic system.     

Distinguishing Parkinson's disease and essential tremor with transcranial sonography

Objectives – Until today there is no reliable test that can clearly distinguish Parkinson’s disease (PD) from the essential tremor (ET). Our aim was to determine the usefulness of the transcranial sonography (TCS) in the differential diagnosis of the PD and ET as well as the interobserver reliability for this method. Methods – Transcranial sonography of substantia nigra and clinical examination were performed on 80 PD patients, 30 ET patients, and 80 matched controls by two independent physicians. Results – Bilateral SN hyperechogenicity over the margin of 0.20 cm² was found in 91% of PD patients, 10% of healthy subjects, and in 13% patients with ET. Interobserver agreement for this method was significant (Student’s t‐test, P = 1.000). Conclusions – Substantia nigra hyperechogenicity on TCS is a highly specific finding of PD, where in healthy individuals or in ET patients, it might correspond to an increased risk of developing PD later in life or might also be because of the impairment of nearby area of nucleus ruber in ET patients, as suggested by positron emission tomography studies. TCS may serve as a practical and sufficiently sensitive neuroimaging tool in PD diagnoses and in distinguishing it from ET; its repeatability and accuracy might add to its practical value.     

经颅超声技术在抑郁症及神经变性疾病伴抑郁中的应用

本文目的是对经颅超声技术(TCS)在抑郁症及神经变性疾病伴抑郁中的应用进行综述,以期为抑郁症及神经变性疾病伴抑郁的临床诊断提供新的方向。TCS在抑郁症患者可表现中缝低回声,在神经变性疾病伴抑郁患者中也出现了特异性表现。本文对TCS在抑郁症及神经变性疾病伴抑郁中的应用进行探讨。     

Right-to-left-shunts detected by transesophageal echocardiography and transcranial Doppler sonography

BACKGROUND: Transesophageal echocardiography (TEE) and transcranial Doppler sonography (TCD) can identify right-to-left-shunts that predispose to paradoxical embolism. In a large cohort we compared the results of both techniques. METHODS: 222 patients were investigated by both techniques using the contrast agent Echovist-300 and performing each test once without and once with the Valsalva maneuver (VM). RESULTS: TEE-proven right-to-left-shunts were detected by TCD with a high sensitivity of 94%. In addition, TCD revealed shunts not noted during TEE in about 20% of all patients studied. These shunts are in general smaller than those concordantly identified; however, 9% of the patients without a TEE-proven shunt presented with a shunt that allows a considerable amount of contrast medium to pass. There were 12% more microbubbles detected in the right middle cerebral artery than in the left middle cerebral artery during the TCD test performed with VM, but not during the TCD test performed without VM. CONCLUSIONS: Contrast-enhanced TEE and TCD are complementary methods in the assessment of stroke and stroke-prone patients. The side difference of microbubbles may indicate a selective streaming of cardiac emboli during VM.     

Predictive value of transcranial sonography in the diagnosis of Parkinson's disease.

Transcanial sonography (TCS) is increasingly applied in the diagnosis of Parkinson's disease (PD), but investigator bias may influence the results of examination. Blinding the sonographer to the clinical diagnosis of 42 PD patients and 35 controls, we obtained a positive predictive value of 85.7% and a negative predictive value of 82.9% in the diagnosis of PD solely by interpreting the results of TCS, indicating that TCS is a valuable additional tool in the diagnosis of PD.     

Detection of presymptomatic Parkinson's disease: combining smell tests, transcranial sonography, and SPECT.

Olfactory loss is among the early signs of Parkinson's disease (PD). We investigated whether "idiopathic" olfactory dysfunction might relate to signs of nigral degeneration. Olfactory tests were combined with transcranial sonography of the substantia nigra and single photon emission computed tomography (SPECT) imaging. Thirty patients diagnosed with idiopathic olfactory loss participated. Eleven of these patients exhibited an increased echogenicity of the SN in the transcranial sonography. In 10 of these 11 patients, SPECT scans with (123)I-FP-CIT were performed. Median uptake ratios in the basal ganglia were pathological in 5 patients, 2 patients exhibited borderline findings, and 3 patients had normal results. Considering patients with idiopathic olfactory dysfunction, noninvasive transcranial sonography seems to be helpful in identifying patients potentially at risk to develop PD. Longitudinal follow-up studies are necessary to estimate the ratio of patients with dopaminergic cell loss in the basal ganglia who will develop PD in the future.     

重复经颅磁刺激治疗帕金森病后抑郁的疗效观察

目的观察重复经颅磁刺激(rTMS)对帕金森病(PD)后抑郁的临床疗效。方法将我院收治的68例PD后抑郁的患者随机分为2组,对照组给予常规抗PD治疗药物,治疗组在对照组治疗基础上联合rTMS治疗,采用汉密尔顿抑郁量表(HAMD)及统一帕金森病评定量表(UPDRS)对治疗前后2组患者抑郁状态及生活、运动功能进行对比。记录治疗组患者rTMS治疗的不良反应。结果治疗组治疗前后HAMD及UPDRS评分显著降低;治疗组HAMD评分较对照组显著降低(P<0.05);治疗组不良反应轻微。结论 rTMS治疗PD后抑郁安全有效,值得临床推广。     

Combination of transcranial sonography, olfactory testing, and MIBG myocardial scintigraphy as a diagnostic indicator for Parkinson's disease

Background: Appropriate diagnostic biomarkers are useful for improving speed and accuracy of a diagnosis. Substantia nigra (SN) hyperechogenicity visualized by transcranial sonography (TCS), olfactory dysfunction, and the reduced uptake of ¹²³I‐metaiodobenzylguanidine (MIBG) in myocardial scintigraphy have been suggested as potential biomarkers for the identification of Parkinson’s disease (PD). Objectives: To evaluate the diagnostic potential of these tests and to determine whether combining them increases their diagnostic power. Methods: Subjects were 44 patients with clinically diagnosed PD and 36 healthy controls. TCS of the SN, the odor stick identification test for Japanese (OSIT‐J), and MIBG myocardial scintigraphy were conducted. Results: Eleven patients with PD (25%) and four controls (11%) were excluded because of an insufficient acoustic temporal bone window in the TCS. Thus, 33 patients with PD and 32 healthy controls were finally included. The diagnostic sensitivity of TCS, OSIT‐J, and MIBG myocardial scintigraphy was 78.8%, 84.8%, and 60.6%, respectively. The specificity of TCS and OSIT‐J was 93.8% and 78.1%, respectively. The combination of TCS of the SN and OSIT‐J substantially increased the sensitivity to a sufficient level for discriminating patients with PD from controls. Conclusion: TCS of the SN and olfactory testing play complementary roles in increasing diagnostic power in PD. As both tests are easy to perform, noninvasive, and inexpensive, the combination of TCS of the SN and olfactory testing may contribute to early and accurate diagnosis of PD.     

Evaluation of basal ganglia, brainstem raphe and ventricles in bipolar disorder by transcranial sonography

Transcranial brain sonography (TCS) has become a reliable and sensitive diagnostic tool in the evaluation of extrapyramidal movement disorders. Alterations of brainstem raphe (BR) have been depicted by TCS in major depression but not in bipolar disorder. The aim of our study was to evaluate BR echogenicity depending on the different conditions of bipolar patients. Echogenicities of dopaminergic basal ganglia structures were assessed for the first time in bipolar disorder. Thirty-six patients with bipolar I disorder (14 depressed, 8 manic, 14 euthymic) were compared to 35 healthy controls. Echogenicities were investigated according to the examination protocol for extrapyramidal disorders using a Siemens Sonoline? Elegra system. The sonography examiner was blinded for clinical rating scores. Six patients (16.7%) showed hyperechogenicity of the substantia nigra. The raphe was hypoechogenic in 13 (36.1%) of the patients. No significant differences were seen between the subgroups. Compared to the control group, frequency of altered echogenicities did not reach statistical significance. The width of third ventricle was significantly larger in the patient group (3.8±-2.1 mm vs. 2.7±1.2 mm). Depressed bipolar patients with reduced BR echogenicity showed significantly higher scores on the Hamilton Depression Rating Scale as well as the Montgomery-?sberg Depression Rating Scale. In contrast to unipolar depression, sonographic findings of bipolar patients may generally indicate structural integrity of mesencephalic raphe structures. If bipolar disorder coexists with hypoechogenic raphe structure, depressive symptoms are more severe.     

Vulnerability of the nigrostriatal system as detected by transcranial ultrasound.

OBJECTIVE: To assess the incidence of a hyperechogenic substantia nigra (SN) by transcranial sonography (TCS) in healthy people and to evaluate whether an enlarged hyperechogenic SN area is associated with functional impairment of the nigrostriatal system. BACKGROUND AND METHODS: Until now, preclinical impairment of the nigrostriatal system could be identified only by functional neuroimaging techniques such as PET in selected groups of patients. TCS is a new, noninvasive ultrasound technique that has demonstrated an increased echogenicity of the SN in patients with PD, whereas in most healthy individuals, the SN is either barely detectable or undetectable by TCS. RESULTS: Of 330 healthy volunteers, 8.6% exhibited an increased echogenicity of the SN. From these, 10 clinically healthy individuals with distinct unilateral or bilateral hyperechogenic signals in the SN region (SN area above 0.25 cm2) underwent comprehensive motor testing, neuropsychological assessment, MRI, and [18F]-dopa PET examination. With regard to motor functions, these individuals did not differ from 10 age- and sex-matched controls with a low echogenic SN and an area of echogenic signals below 0.2 cm2. Enlargement of hyperechogenic areas in the 10 healthy individuals was associated with a marked decrease in the accumulation of [15F]-dopa in the caudate nucleus and putamen. CONCLUSIONS: Substantia nigra hyperechogenicity appears to indicate a functional impairment of the nigrostriatal system. Transcranial sonography may be a suitable method of identifying persons at risk of nigrostriatal alterations, making possible the introduction of early neuroprotective therapy.     

Differentiation of Parkinson's disease and atypical parkinsonian syndromes by transcranial ultrasound

Neuroimaging is known to complement clinical findings in the diagnostic work up of parkinsonian syndromes. Recently, transcranial ultrasound was reported to have a high diagnostic yield in differentiating idiopathic Parkinson's disease (IPD) from atypical parkinsonian syndromes. This report summarises the sonographic findings of 102 patients with IPD, 34 patients with multiple system atrophy, and 21 patients with progressive supranuclear palsy. Increased echogenicity of the substantia nigra is predictive for IPD whereas a low echogenic substantia nigra, particularly when combined with a hyperechogenic lentiform nucleus, strongly suggests an atypical Parkinsonian syndrome. The underlying causes for the differential echo pattern of the substantia nigra remain unknown.     

Escitalopram for major depression in Parkinson's disease: an open-label, flexible-dosage study

Depression and antidepressant use are common in Parkinson's disease, but the benefit of selective serotonin reuptake inhibitor (SSRI) treatment in this population has not been established. The authors treated 14 Parkinson's disease patients with major depression with escitalopram in an open-label study. Although treatment was well tolerated and correlated with a significant decrease in Inventory of Depressive Symptomatology score, response and remission rates were only 21% and 14%, respectively. However, half of the subjects met Clinical Global Impression-Improvement criteria for response. In Parkinson's disease, either SSRIs may have limited antidepressant effects, or the use of existing depression diagnostic and rating instruments may be problematic.     

Evaluation of the vertebrobasilar-posterior system by transcranial color duplex sonography in adults.

BACKGROUND AND PURPOSE: The transcranial color duplex sonography technique was applied to the vertebrobasilar-posterior system to provide normal data for clinical application. METHODS: The intracranial posterior circulation was studied in 49 healthy volunteers (mean +/- SD age, 35 +/- 12 years) by a transcranial and suboccipital approach with a 2.0-MHz sector transducer of a computed sonography system. RESULTS: The posterior cerebral artery and the vertebrobasilar system were depicted clearly in the color Doppler mode. Pulsed Doppler signals could be recorded in the posterior cerebral (100%), basilar (92%), and vertebral arteries (89%). The following normal values were provided for all vessels: systolic peak, end-diastolic maximum, time-averaged, and time-averaged maximum velocities; resistance and pulsatility indexes; and a spectral broadening index. Mean +/- SD values were 45.9 +/- 9.6, 45.5 +/- 10.8, and 39.2 +/- 10.6 cm/sec for time-averaged maximum velocity, and 28.3 +/- 6.5, 30.6 +/- 7.2, and 24.7 +/- 8.4 cm/sec for time-averaged velocity in the posterior cerebral, basilar, and vertebral arteries, respectively. In a reproducibility study, duplex measurements of the posterior cerebral arteries were repeated in 27 subjects. The correlation between the two examiners was high (r = 0.56, p less than or equal to 0.0001 for time-averaged maximum velocity). CONCLUSIONS: Color duplex sonography of the vertebrobasilar-posterior system is a new, noninvasive, bedside investigative technique. It permits visualization of artery flow in real time, relating these to adjacent brain and cranial structures, as well as angle-corrected duplex measurement of "true" flow velocities at defined sites of the vessels. Thus, it will open new diagnostic possibilities in disorders of the posterior circulation.     

An open study of repetitive transcranial magnetic stimulation in treatment-resistant depression with Parkinson's disease.

OBJECTIVE: Major depression is a common concomitant of chronic central nervous system disorders, notably Parkinson's disease (PD). Repetitive transcranial magnetic stimulation (rTMS) has been investigated as a potential treatment for depression in PD and for the movement disorder of PD, but comprehensive testing in multiple areas of performance has seldom been carried out within a single study. We studied the effect of left dorsolateral prefrontal rTMS on several different functional domains. METHODS: Fourteen PD patients with treatment-resistant depression entered an open, 10-day inpatient study of 10-Hz rTMS, undergoing extensive psychiatric, neuropsychological, and motor testing from baseline to 6 weeks after treatment. Motor testing included a defined "off" state. RESULTS: rTMS was well tolerated. Highly significant improvement in depression scores was seen 3 days and 3-6 weeks after treatment. Improvement was also found in anxiety, movement scores (especially in the off state), and some neuropsychological measures. We found no evidence of increased risk from rTMS in this population. CONCLUSIONS: Further controlled trials of rTMS in PD appear worthwhile, and should include a defined "off" state. SIGNIFICANCE: TMS may be beneficial for depressed PD patients in multiple functional domains.     

早期帕金森病伴抑郁患者边缘系统白质微结构的改变

目的探讨早期帕金森病(PD)伴发抑郁症状(PD with depression,PDD)患者边缘系统脑白质微结构的改变,为临床早期诊断PDD提供依据。方法纳入早期原发性PD患者16例,其中PDD患者7例,不伴发抑郁症状(PD without depression,PDND)9例,选取同期年龄、性别、受教育程度匹配的健康志愿者16例。所有受试者均行汉密顿抑郁量表(HAMD)、统一帕金森病评定量表运动部分(UPDRS PartⅢ)、H&Y分期评定及MRI+DTI检查,测量边缘系统各感兴趣区域(region-of-interest,ROI)各向异性分数(fractional anisotropy,FA)及平均弥散系数(average diffusion coefficient,ADC),进行统计分析。结果 PD组较健康对照组HAMD评分高(P<0.05),除右丘脑背内侧外,PDD组较健康对照组各ROI区FA值均有下降(P<0.05);PDD组左额叶眶部、双侧前扣带束及左丘脑背内侧FA值较PDND组下降显著(P<0.01);3组间各ROI区ADC值无统计学差异。结论早期PD伴抑郁患者边缘系统已出现广泛白质微结构的异常改变,其中左额叶眶部、双侧前扣带束及左丘脑背内侧FA值的下降,对PDD患者的早期诊断有重要参考价值。     

New component of the limbic system: Marginal division of the neostriatum that links the limbic system to the basal nucleus of Meynert

The limbic system refers to a group of connected neural regions that are associated with motivation, learning, and memory. The marginal division (MrD) is a zone located at the caudal border of the neostriatum in mammalian brains that has been shown to be involved in learning and memory. In a previous study, c-fos expression showed functional connections between the MrD, basal nucleus of Meynert (NBM) and limbic system (Shu et al., 1988a, 1999). In the present study, to explore the relationship between these regions, the expression of limbic system-associated membrane protein (LAMP) was investigated using molecular and immunohistochemical methods. Synaptic and functional connections between the MrD and the NBM were studied also using tract tracing, electron microscopic and behavioral methods. LAMP is thought to be a marker of the limbic system and expression of LAMP protein and mRNA was observed in both the MrD and the limbic system. From such results, it is concluded that the MrD is a new component of the limbic system. Fibers from the MrD were observed projecting and synapsing on cholinergic neurons of the NBM. As reduction of learning and memory was induced by lesioning the projection from the MrD to the NBM, it would seem that the MrD modulates the learning and memory function of the NBM. In conclusion, the results of these studies suggest that the MrD is a new component of the limbic system, and there are functional and structural connections between the MrD, NBM and limbic system. The MrD seems to act as a link between the limbic system and the NBM, and plays a role in learning and memory.