Transcranial color-coded sonography helps differentiation between idiopathic Parkinson's disease and vascular parkinsonism

Abstract Background Recently, transcranial color-coded sonography (TCCS) has been found to have a diagnostic value in patients with idiopathic Parkinson's disease (IPD), which displays increased hyperechogenicity at the substantia nigra (SN). Objective To use TCCS, to assess the difference in SN hyperechogenicity and intracranial hemodynamics among subjects with IPD, vascular parkinsonism (VP) and controls. Methods Eighty IPD and 30 VP patients, and 60 controls were recruited into this study. The hyperechogenicity area at the SN and midbrain were calculated by encircling the outer circumference from the ipsilateral temporal window, using TCCS in each subject. The hemodynamics of intracranial large arteries, including flow velocity and pulsatility index (PI), were also measured. Results The presence of SN hyperechogenicity was significantly higher in the IPD patients than in the VP patients and controls (84% vs. 20% & 5%, respectively, p < 0.001). In IPD patients, the SN hyperechogenicity was correlated with the neurological severity and disease duration. Twenty-five (66.7%) VP patients had obvious vascular abnormality, as seen in TCCS study. The mean PI was significantly more elevated in the VP patients than those in the IPD patients and controls (all p < 0.05), but there was no significant difference of flow velocities among the VP, IPD patients and controls. Conclusion TCCS, combining B-mode imaging for SN echogenicity and trancranial Doppler for intracranial hemodynamics, is a useful diagnostic tool in the differentiation between IPD and VP. These findings also suggest that multiple subcortical vascular lesions may damage the basal ganglia and thalamocortical circuit and result in parkinsonism features in VP patients.     

Transcranial brain sonography findings in clinical subgroups of idiopathic Parkinson's disease.

To investigate whether transcranial brain sonography (TCS) discriminates different courses of idiopathic Parkinson's disease (PD), 101 patients with clinically definite PD were studied. In four patients, TCS was not possible due to insufficient acoustic temporal bone windows. Substantia nigra (SN) hyperechogenicity was found in 96% of assessable patients. Larger SN echogenic size correlated with younger age at PD onset (Spearman correlation, r = -0.383; P < 0.001), but not with age, PD duration, or severity. Marked bilateral SN hyperechogenicity indicated early-onset rather than late-onset PD, and akinetic-rigid (AR) or mixed-type (MX) PD rather than tremor-dominant PD. SN echogenic sizes were larger contralateral to the clinically more affected side in AR PD and MX PD patients. Reduced echogenicity of brainstem raphe was associated with depression (RR = 1.61; 95% CI = 1.05-2.46; P = 0.044) but not with other clinical features. Caudate nucleus hyperechogenicity was, independently from PD duration, related to drug-induced psychosis (RR = 2.40; CI = 1.36-4.22; P = 0.001), but not to motor fluctuations. Lenticular nucleus hyperechogenicity indicated AR PD rather than tremor-dominant PD (RR = 1.44; CI = 1.11-1.86; P = 0.040). Frontal horn dilatation > 15.4 mm (mean of bilateral measurements) indicated increased risk of dementia (RR = 4.11; CI = 1.51-11.2; P = 0.001). We conclude that TCS displays characteristic changes of deep brain structures in different clinical manifestations of PD.     

Transcranial sonography findings in Parkinson's disease

Interest in diagnostic biomarkers that improve identification of Parkinson's disease (PD) in the early stages has been recently increasing. Accurate diagnosis of PD is currently a challenge for clinical neurologists. In addition, recent advances in basic research towards neuroprotective strategies for PD are increasingly highlighting the need for diagnostic biomarkers that improve identification of PD in the early stages. As such, substantia nigra hyperechogenicity visualized by transcranial sonography (TCS) has gained increasing attention and has been implemented in PD diagnosis globally. As substantia nigra hyperechogenicity offers unique information supplementary to those provided by other neuroimaging techniques, and this echofeature is stable during the disease course, it is very helpful in early and differential diagnosis of PD. The pathophysiologic conditions underlying this echofeature are not fully understood; however, it maybe associated with increased amounts of iron. It should be reminded that there are several limitations in conducting TCS. The main limitation is that in Japanese subjects the rate of temporal bone window sufficient for an adequate sonographic analysis prominently decreases with advancing age, particularly in females. Another limitation is that measurements may vary between two laboratories. Therefore, investigators are required to generate their own reference values. Despite these limitations, TCS can be recommended as a useful technique for the diagnosis of PD owing to its fast and easy use, low cost, and noninvasive nature. This review summarizes the TCS technique, the typical findings, and their value in the diagnosis and differential diagnosis of PD.     

Transcranial sonography and functional imaging in glucocerebrosidase mutation Parkinson disease

BackgroundHeterozygous glucocerebrosidase (GBA) mutations are the leading genetic risk factor for Parkinson disease, yet imaging correlates, particularly transcranial sonography, have not been extensively described.MethodsTo determine whether GBA mutation heterozygotes with Parkinson disease demonstrate hyperechogenicity of the substantia nigra, transcranial sonography was performed in Ashkenazi Jewish Parkinson disease subjects, tested for the eight most common Gaucher disease mutations and the LRRK2 G2019S mutation, and in controls. [¹⁸F]-fluorodeoxyglucose or [¹⁸F]-fluorodopa positron emission tomography is also reported from a subset of Parkinson disease subjects with heterozygous GBA mutations.ResultsParkinson disease subjects with heterozygous GBA mutations (n = 23) had a greater median maximal area of substantia nigral echogenicity compared to controls (n = 34, aSNmax = 0.30 vs. 0.18, p = 0.007). There was no difference in median maximal area of nigral echogenicity between Parkinson disease groups defined by GBA and LRRK2 genotype: GBA heterozygotes; GBA homozygotes/compound heterozygotes (n = 4, aSNmax = 0.27); subjects without LRRK2 or GBA mutations (n = 32, aSNmax = 0.27); LRRK2 heterozygotes/homozygotes without GBA mutations (n = 27, aSNmax = 0.28); and GBA heterozygotes/LRRK2 heterozygotes (n = 4, aSNmax = 0.32, overall p = 0.63). In secondary analyses among Parkinson disease subjects with GBA mutations, maximal area of nigral echogenicity did not differ based on GBA mutation severity or mutation number. [¹⁸F]-fluorodeoxyglucose (n = 3) and [¹⁸F]-fluorodopa (n = 2) positron emission tomography in Parkinson disease subjects with heterozygous GBA mutations was consistent with findings in idiopathic Parkinson disease.ConclusionsBoth transcranial sonography and positron emission tomography are abnormal in GBA mutation associated Parkinson disease, similar to other Parkinson disease subjects.     

Transcranial brain sonography findings related to neuropsychological impairment in multiple sclerosis

Cognitive dysfunction, fatigue and mood disorder contribute to the neuropsychological impairment that is common in multiple sclerosis (MS). The present paper reviews application of transcranial brain sonography (TCS) in MS patients and TCS findings related to neuropsychological dysfunction. TCS is a new neuroimaging method displaying tissue echogenicity of the brain through the intact skull. Whereas the cortex can not be discriminated from the subcortical white matter with TCS, subcortical brain structures such as ventricles and basal ganglia can be adequately displayed. Even though TCS proved sensitive and reliable in measuring widths of third and lateral ventricles in a number of neurodegenerative diseases, relatively few TCS studies on MS patients have been reported. Data of these studies suggest a good correlation of cognitive dysfunction and width of third ventricle which can be measured reliably with TCS. Moreover, abnormal TCS findings of basal ganglia were associated with cognitive impairment. However, TCS findings of midbrain structures, basal ganglia and ventricles did not correlate with fatigue or depression in MS patients. TCS has the advantages of low costs, short investigation times and unlimited repeatability. The use of third-ventricle and basalganglia TCS for predicting and monitoring neuropsychological impairment in MS patients, however, needs to be elucidated in further studies.     

Transcranial brain sonography findings related to neuropsychological impairment in multiple sclerosis

Journal of Neurology - Cognitive dysfunction, fatigue and mood disorder contribute to the neuropsychological impairment that is common in multiple sclerosis (MS). The present paper reviews...     

Transcranial brain sonography in Parkinson's disease with restless legs syndrome

Substantia nigra (SN) hyperechogenicity assessed by transcranial brain sonography (TCS) is a characteristic finding in idiopathic Parkinson's disease (PD). In contrast, SN hypoechogenicity on TCS has been recently demonstrated in restless legs syndrome (RLS). RLS is one of the most common sleep problems in PD, but the pathophysiologic relationship between these two disorders has not been thoroughly elucidated. We compared the SN echogenicities of PD patients with and without RLS to investigate whether comorbid RLS in PD affects SN echogenicity and to explain the echogenic differences between idiopathic RLS (iRLS) and secondary PD–related RLS (pRLS). Sixty‐three PD patients (median age 64.6 ± 10.6 years), 40 iRLS patients (53.1 ± 11.7 years), and 40 healthy controls (69.1 ± 2.3 years) were enrolled in our study. All subjects answered a sleep questionnaire and underwent TCS. PD patients were subdivided into two groups, PD with RLS (PD+RLS, n = 26) and PD without RLS (PD‐RLS, n = 37), and the sonographic findings of each group were compared. Although significant hyperechogenicity was detected in both the SN and SN/midbrain ratios in both PD subgroups compared with the controls and the iRLS group (P < 0.001), there were no significant differences in SN echogenicity between the PD+RLS and PD‐RLS groups. Meanwhile, iRLS patients showed significant SN hypoechogenicity. In conclusion, comorbid RLS in PD did not have an impact on the sonographic SN findings. These results suggest that the pathogenesis of pRLS and iRLS involve different mechanisms. Further study will be required to clarify the association between RLS and PD. © 2010 Movement Disorder Society     

Transcranial sonography in Wilson's disease

Transcranial sonography (TCS) has been recently recognized as a reliable and sensitive tool in detecting basal ganglia (BG) abnormalities in several movement disorders, where different patterned hyperechogenic lesions were demonstrated. The aim of this study was to investigate changes in TCS in a larger group of clinically stable patients with Wilson's disease (WD), and to correlate them with demographic and clinical data. TCS was conducted in 54 consecutive, clinically stable patients with WD who were classified as predominantly neurologic or hepatic form of the disease and were adequately assessable by TCS from both sides. TCS revealed significantly higher prevalence of SN (p = 0.007) and LN hyperechogenicity (0.001) in WD patients when compared to controls. Moderate to marked SN hyperechogenicity was found in 31.5% of WD patients (in 42% and 7% of those with neurologic and hepatic form of WD, respectively) and in 8% of healthy controls. Disease severity correlated with the hyperechogenicity of SN (r = 0.303; p = 0.029) and with the width of the third ventricle (r = 0.351; p = 0.011). There is only one report of TCS in WD previous to our study. Both studies proved the ability of TCS to detect accumulation of copper and probably other trace metals, such as iron and manganese, in the BG of WD patients.     

运动障碍性疾病的经颅脑实质超声诊断

运动障碍性疾病的诊断与鉴别诊断长期以来一直是临床医学的难点,主要根据疾病进展到一定阶段后出现的症状与体征作出诊断,客观指标极少,明确诊断需要病理结果。近年来,欧洲国家开展一项新型检查方法即经颅脑实质超声检查,从最初对帕金森病的诊断到用于其他运动障碍性及神经变性疾病的辅助诊断,具有无创、简易、检查时问短,以及便于早期诊断等优势。本文将从经颅脑实质超声的发展过程、对运动障碍性疾病的诊断原理、在运动障碍性疾病的应用,以及临床应用优势和局限性等方面简述这一领域的发展过程和研究进展。     

Transcranial sonography findings in welding‐related Parkinsonism in comparison to Parkinson's disease

The pathogenetic relationship of welding‐related Parkinsonism (WP) and idiopathic Parkinson's disease (PD) is a matter of debate. In the present study, we compared transcranial sonography (TCS) findings in patients with WP and PD. Two male patients with WP, who had developed levodopa‐resistant akinetic‐rigid Parkinsonism without ongoing progression after having worked as welders for many years in Chilean mines in confined spaces without adequate ventilation, and three age‐matched male patients with clinically definite akinetic‐rigid PD were studied with TCS in a random order by two investigators blind to clinical diagnoses. In both WP patients, normal echogenicity of substantia nigra was found whereas all PD patients exhibited marked substantia nigra hyperechogenicity, previously reported as a characteristic TCS finding in idiopathic PD. In contrast, lenticular nucleus was hyperechogenic in both WP patients but only in one of the PD patients. TCS findings suggest a different pathophysiology of Parkinsonism in WP and PD patients. © 2007 Movement Disorder Society     

早发性帕金森病患者经颅超声的表现

目的 研究早发性帕金森病(EOPD)患者经颅超声(transcranial sonography,TCS)的表现.方法 招募符合入选标准的EOPD患者和性别、年龄匹配的正常对照者,分别进行TCS检测.对受试者的黑质信号进行半定量分级测评,同时测定第三脑室的宽度.结果 两组间黑质强回声分级有极强的显著性差异.黑质强回声分级与患者的年龄、发病年龄、病程及病情严重程度不相关.两组间第三脑室宽度无显著性差异.结论 和以往关于LOPD患者的研究结果类似,EOPD患者也能发现明显的黑质异常强回声.其强回声分级与患者年龄、发病年龄、病程及病情严重程度不相关.EOPD患者组无明显第三脑室增宽.     

晚发型帕金森病经颅超声的表现

目的 研究晚发型帕金森病(LOPD)患者经颅超声(transcranial sonography,TCS)的表现.方法 招募符合入选标准的LOPD患者和年龄匹配的正常对照者,分别进行TCS检测.对于检测成功的受试者的黑质异常信号进行半定量分级测评,同时测定第三脑室的宽度.结果 TCS检查在老年女性中成功率很低.两组间黑质强回声分级有极强的显著性差异.黑质强回声分级与患者的年龄、发病年龄、病程及病情严重程度不相关.两组间第三脑室宽度无显著性差异.结论 TCS检查在老年女性中应用受限制.明显的黑质异常强回声可能是LOPD患者的特征性表现.其强回声分级与患者年龄、发病年龄、病程及病情严重程度不相关.晚发型帕金森病患者组无明显第三脑室增宽.

Abstract：

Objective To investigate the characteristic features of transcranial sonography (TCS) in patients with late-onset Parkinson' s disease (LOPD). Methods We enlisted some LOPD patients and age-matched normal controls according to special criteria, and detected them by TCS. The obtained images of the subjects whose images could offer analyzing substantia nigra (SN) hyperechogenicity with sufficient resolution were evaluated. We used semi-qualitative estimation criteria to assess SN hyperechogenicity and also measured the widths of the third ventricles. Results There was a high rate of recording failure of the SN in older females. Significant SN hypereehogenicity was observed in LOPD patients group.There was no correlation between the degree of SN hyperechogenicity and patients' age, onset age, duration of illness, and the severity of condition. There was no significant difference of the widths of the third ventricles between groups. Condusions The recording failure in aged females may limit the clinical potential of TCS. SN hyperechogenicity maybe the characteristic features in LOPD patients. There was no correlation between the degree of SN hyperechogenicity and patients'age,onset age, duration of illness, and the severity of condition. The widths of the third ventricles in LOPD patients group were not increased significantly.     

Olfaction differentiates parkin disease from early-onset parkinsonism and Parkinson disease

The authors studied whether olfactory dysfunction is present in parkin disease using the University of Pennsylvania Smell Identification Test (UPSIT). The mean UPSIT score in parkin patients was 27.3 (95% CI 24.4 to 30.2). This did not differ from the normal group mean of 29.4 (95% CI 28.0 to 30.7; p = 0.22) but was higher than the Parkinson disease group (mean 14.3; 95% CI 12.2 to 19.5; p < 0.0001) and the parkin-negative group (mean 17.1; 95% CI 14.8 to 16.3; p < 0.0001) values. Parkin disease may be a distinct and separate entity from Parkinson disease.     

Search for viral particles and virus-specific products in idiopathic Parkinson disease brain material

Virological studies were performed on brain material from 9 patients with idiopathic Parkinson disease and 3 matched controls. Electron microscopy and indirect immunofluorescent study were carried out directly on autopsy material from substantia nigra, caudate nucleus, and hypothalamus and on primary tissue culture explants of these brain areas grown alone or in cocultivation with virus-susceptible indicator cell lines. All studies were negative for the presence of viral particles, viral inclusions, or cellular changes suggestive of virus infection. All materials were negative for antigens of herpes simplex type 1, influenza A/NWS, and measles (Edmonston strain) viruses. Within the limits of these tehcniques, there is no evidence at this time that viruses are an important etiological agent in idiopathic Parkinson disease.     

POLG1 in idiopathic Parkinson disease

We studied POLG1 in 140 UK patients with idiopathic Parkinson disease (PD) and 279 Italian patients with PD and compared them to a UK control group (n = 207) and an Italian control group (n = 285). Our observations do not support a role for common POLG1 genetic variants in PD and indicate that dominant POLG1 mutations are a rare cause of parkinsonism in the general population.     

Neuroimaging of Parkinson’s disease and atypical parkinsonism

The basal ganglia and its associated circuitry can be assessed with a variety of neuroimaging methods that can provide information regarding specific neurotransmitter systems, the functional activity of brain regions, and the structural integrity of these regions. In Parkinson’s disease (PD) and related atypical parkinsonian syndromes (APS), these imaging methods may be useful for many reasons, including aiding in differential diagnosis and measuring the efficacy of new therapies. This paper reviews recent developments in the application of neuroimaging to the assessment of PD and related APS.