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 of the substantia nigra in patients with Parkinson's disease

Journal of Neurology - Transcranial sonography (TCS) of the substantia nigra (SN) is becoming a tool for the diagnosis of Parkinson's disease (PD), particularly in the early phase of illness....     

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 patients with Parkinson's disease with glucocerebrosidase mutations

ObjectivesThe aim of this study was to search for possible differences in the findings of transcranial sonography (TCS) between groups of patients with glucocerebrosidase (GBA)-associated Parkinson's disease (PD) (4 patients with Gaucher disease type 1 and parkinsonism [GD+PD+] and 18 PD patients with heterozygous GBA mutations; [GBA+PD+]) and groups of 12 patients with Gaucher disease type 1 and no signs of parkinsonism (GD+PD?), 9 asymptomatic carriers of heterozygous GBA mutations (GBA+PD?), 32 sporadic PD patients (sPD), and 43 healthy controls.ResultsIn all groups of patients, except asymptomatic carriers of heterozygous GBA mutations (mean ± SD: 0.16 ± 0.03 cm²), the maximal areas of substantia nigra hyperechogenicity (aSN-max) was higher (GD+PD+: 0.28 ± 0.15 cm²; GD+PD?: 0.18 ± 0.06 cm²; GBA+PD+: 0.27 ± 0.06 cm²; sPD: 0.28 ± 0.10 cm²) when compared to controls (0.12 ± 0.08 cm²) (p = 0.001). In GBA-associated PD (GD+PD+ and GBA+PD+) and sPD, aSNmax values were very similar. Moderate or marked SN hyperechogenicity was present in 87.5% of sPD patients and in 83% of PD patients with heterozygous GBA mutations, but in only 11.6% of controls, and in 22.2% and 33.3% of patients from GBA+PD? and GD+PD? groups, respectively (p < 0.001). The prevalence of interrupted or missing echogenicity of the brainstem raphe differed between the groups (p = 0.046), while no difference was observed in the diameter of the third ventricle.ConclusionsTCS findings in GBA-associated PD were consistent to those of patients with sporadic PD.     

帕金森病患者经颅脑实质超声所见与临床评价

目的探讨经颅脑实质超声中发现的中脑黑质高回声与帕金森病(PD)的关系。方法连续入选2010~2013年中日友好医院门诊和住院诊断的123例PD患者及78例健康对照者,行经颅脑实质超声检查,测量黑质区域强度Ⅲ级的信号面积、第三脑室宽度及基底节区有无异常信号。并对123例PD患者进行统一帕金森病评定量表(UPDRS)评分、HoehnYahr分级。最后分析黑质高回声面积与UPDRS评分、HoehnYahr分级的相关性。结果最后入组89例PD患者及60例健康对照者。89例PD患者中,81例患者黑质高回声面积≥0.2 cm2;60例健康志愿者中,5例黑质高回声面积≥0.2 cm2。PD患者组的黑质高回声面积与健康对照组有明显差异。Pearson相关性分析发现黑质高回声面积的大小与患者发病年龄及病程长短无关系;较大侧黑质高回声与UPDRS评分的总分、第Ⅲ部分及HoehnYahr分级有明显相关性。黑质高回声面积在临床症状(UPDRSⅢ)较重的对侧较大。结论我国PD患者中脑黑质高回声是PD的一个特征性标记,其面积大小与PD患者运动症状的严重程度呈正相关,临床上可将经颅脑实质超声作为PD患者诊断的工具之一。     

Transcranial sonography of the substantia nigra and MIBG myocardial scintigraphy: complementary role in the diagnosis of Parkinson's disease

Both transcranial sonography (TCS) of the substantia nigra (SN) and metaiodobenzylguanidine (MIBG) myocardial scintigraphy have been determined to be useful for the diagnosis of Parkinson's disease (PD). In the present study, we performed both tests in 65 consecutive Japanese patients with idiopathic PD. In 30 PD patients (46.2%), the midbrain was adequately displayed by TCS allowing quantitative measurements of SN hyperechogenic areas. No significant correlation was found between the area of SN echogenicity and the reduction of myocardial uptake of MIBG. However, if the cut-off value was appropriately set, 29 patients (97%) were identified as abnormal by combined TCS and MIBG myocardial scintigraphy. Since TCS and MIBG myocardial scintigraphy can distinctively detect PD-related pathological phenomenon, it is expected that the combination of these tests could contribute to an accurate diagnosis of PD.     

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 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 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.     

The differential diagnosis of Parkinson's disease

The diagnosis of Parkinson's disease continues to be challenging with misdiagnosis rates as high as 20–30% in early stages. Such diagnostic inaccuracy is largely due to failure to recognize atypical parkinsonian disorders including multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and dementia with Lewy bodies (DLB). These disorders are characterized by distinctive sets of atypical features that have been incorporated into recent consensus diagnostic criteria. Early diagnosis of atypical parkinsonian disorders is important not only because of prognostic implications, but also because of variable therapeutic targets such as autonomic failure, apraxia or dementia.     

Transcranial sonography in diagnosis of movement disorders

Conventional methods of neuroimaging, such as computed tomography and magnetic resonance imaging, are mostly useful in exclusion of movement disorders with secondary aetiology. Recently, the application of transcranial sonography has been introduced to the diagnosis of extrapyramidal diseases. This valuable technique, with proven usefulness in the field of cerebrovascular events, may reveal some brain parenchymal structures. In this review the most important findings of ultrasonographic abnormalities in the brain, particularly hyperechogenicity of substantia nigra in Parkinson disease, are presented.     

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     

帕金森病早期诊断的生物学标志物

帕金森病是一种慢性进行性中枢神经系统退行性疾病.早在临床前期尚未出现典型临床症状时,帕金森病患者即已出现神经系统退行性病变.因此,如果能在退行性病变早期及时明确诊断并予以治疗,将会减缓疾病进程,提高患者生活质量.虽然目前尚未发现早期诊断帕金森病的理想标志物,但是已有许多生物学标志物具有研究和应用前景.     

Epidemiology, diagnosis and differential diagnosis in Parkinson's disease tremor

The epidemiology of tremor in Parkinson's disease is not well examined. The prevalence of Parkinson's disease is about 100-300 per 100,000, and the majority (70-100%) of these patients may develop tremor during the course of the disorder. The expression of tremor is also influenced by the genetic background of selected patients. On the other hand, Parkinson patients with a predominant tremor phenotype may have a more favourable prognosis in terms of mortality and the development of motor and non-motor complications. The diagnosis of Parkinson tremor is based on a clinical diagnosis of both underlying Parkinson's disease and on the tremor itself. Tremor is a rhythmical, involuntary oscillatory movement of a body part, and includes resting tremor, action tremor including postural and kinetic tremor. The classical type is resting tremor, but other phenotypes may also occur. Misdiagnoses between Parkinson tremor and essential tremor are relatively common. Electrophysiological and functional imaging examinations can be useful in the distinction of the two, but both approaches suffer from some limitations. In general, essential tremor and other tremor forms can be distinguished from Parkinson tremor by their frequency and their expression with different activation.     

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.     

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.     

Functional brain imaging in the differential diagnosis of Parkinson's disease

The accurate diagnosis of idiopathic Parkinson's disease (IPD) is not only important for deciding on treatment strategies and providing a prognosis, but also crucial for studies designed to investigate the aetiology and pathogenesis of parkinsonian disorders. Over recent decades, improvements in the characterisation of the parkinsonian syndromes have led to improvements in clinical diagnostic accuracy; however, clinical criteria alone are not always sufficient to distinguish between IPD and other parkinsonian syndromes, particularly in the early stages of disease and in atypical presentations. Therefore, in addition to the development and implementation of diagnostic clinical assessments, there is a need for available objective markers to aid the physician in the differential diagnosis of IPD. Functional neuroimaging holds the promise of improved diagnosis and allows assessment in early disease. In this review, the use of PET and single photon emission CT in the differential diagnosis of IPD are discussed.