Clinical study of transcranial sonography image characteristics in patients with obstructive sleep apnea.

OBJECTIVE: This study aimed to explore the relationship between patients with obstructive sleep apnea (OSA) from subgroups of varying severity and substantia nigra (SN) hyperechogenicity as well as cerebral blood flow detected by transcranial sonography (TCS). The study also explored if there were differences in damage of the SN and in the cerebral blood flow between the bilateral sides. METHODS: Right-handed men diagnosed with OSA by polysomnography were recruited from August 2018 to August 2020. The included patients were divided into 3 subgroups (mild, moderate, and severe OSA), and all patients underwent TCS. RESULTS: Among the 157 study patients (30 with mild OSA, 25 moderate, and 102 severe), the overall prevalence of SN hyperechogenicity was 15% (23/157). The hyperechogenicity detection rates were 3% (4/157) in the right SN subgroup and 13% (20/157) in the left SN subgroup, which were significantly different. The left side always had reduced blood flow on TCS (P < 0.05). No correlation was observed between the severity of OSA and the detection rates of SN hyperechogenicity (P > 0.05). CONCLUSION: Patients with OSA showed a higher detection rate of SN hyperechogenicity on the left compared with the right side. The left middle cerebral arteries had reduced blood flow, which was consistent with the more severe damage of the left SN. No relationship was observed between the severity of OSA and the detection rate of SN hyperechogenicity or hemodynamic parameters.

Substantia nigra hyperechogenicity in essential tremor and Parkinson's disease: a longitudinal study.

BACKGROUND AND PURPOSE: Essential tremor (ET) and Parkinson's disease (PD) sometimes overlap in their clinical expression with ET preceding PD onset, often leading to misdiagnosis. Transcranial sonography (TCS) has been shown to be a valid and non-invasive diagnostic tool to identify early idiopathic PD and to differentiate it from ET. The purpose of this study was to investigate the relevance of substantia nigra hyperechogenicity in patients with ET. METHODS: A total of 138 patients (79 with PD, 59 with ET) and 50 matched controls underwent TCS examination at baseline. All patients were followed in a 3-year longitudinal assessment. RESULTS: A total of 10 subjects were excluded from the analysis due to the bilateral absence of a temporal acoustic window. During the follow-up period, 11 of the patients with ET developed new-onset parkinsonian features, without fulfilling criteria for PD diagnosis (ET+). Nine patients developed clinical features meeting diagnostic criteria for probable PD (ET-PD). Patients with ET- did not develop parkinsonian features. For each group, the maximum size of the substantia nigra hyperechogenicity was as follows: 5.62 ± 5.40 mm2 in the control group, 19.02 ± 14.27 mm2 in patients with PD, 9.15 ± 11.26 mm2 in patients with ET-, 20.05 ± 13.78 mm2 in patients with ET+ and 20.13 ± 13.51 mm2 in patients with ET-PD. ET-PD maximum values were significantly different from controls. Maximum values in patients with ET+ were different from both controls and patients with ET-. CONCLUSION: Substantia nigra hyperechogenicity in ET seems to represent a risk marker for developing early parkinsonian symptoms or signs in the 3 years following TCS assessment.

Hypoechogenicity of brainstem raphe correlates with depression in migraine patients.

BACKGROUND: Brainstem raphe (BR) hypoechogenicity in transcranial sonography (TCS) has been depicted in patients with major depression (MD) and in depressed patients with different neurodegenerative diseases. But, up to date, the association of BR alterations in TCS with depression in migraineurs has never been reported. This study was to investigate the possible role of BR examination via TCS in migraineurs with depression. METHODS: Forty two migraine without aura (MwoA) patients and 40 healthy controls were recruited. Echogenicity of lentiform nuclei (LN), caudate nuclei (CN), substantia nigra (SN) and brainstem raphe (BR) and width of the frontal horns of the lateral ventricles and the third ventricle were assessed with TCS. The diagnosis of depression was based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders IV (DSM -IV), and the severity of depression was measured by Hamilton Rating Scale for Depression (HAM-D) and Hospital Anxiety and Depression Scale depression subscale (HADS-D). RESULTS: There were no significant differences between migraineurs and controls in the width of frontal horn of the lateral ventricle (p = 0.955), width of third ventricle (p = 0.129) as well as in the echogenicity of SN (p = 0.942), CN (p = 0.053), LN (p = 0.052) and BR (p = 0.677). Here, it seems that more migraineurs were detected with increased echogenecity of CN and LN compared with controls (33.3% versus 15.0% for CN, 19.0% versus 5.0% for LN) though they had no statistical significance. Patients with hypoechogenic BR had significantly higher HAM-D and HADS-D scores than those with normal BR signal (p = 0.000 for both HAM-D and HADS-D), and most (83.33%) migraineurs with depression exhibited hypoechogenic raphe but none (0.00%) of the migraineurs without depression exhibited hypoechogenic raphe (p = 0.000). CONLUSIONS: TCS signal alteration of BR can be a biomarker for depression in migraine but it is not associated with migraine headache itself. LN and CN alterations in TCS may reflect a potential role of them in the pathogenesis of migraine, which needs to be further elucidated.

Fetal ultrasonographic findings including cerebral hyperechogenicity in a patient with non-lethal form of Raine syndrome.

Raine syndrome is a rare osteosclerotic bone dysplasia characterized by craniofacial anomalies and intracranial calcification. Most patients with Raine syndrome are of Arab ancestry and die during the neonatal period. We herein report a Japanese patient with non-lethal Raine syndrome who presented with characteristic cerebral hyperechogenicity and a hypoplastic nose by fetal ultrasonography. She was admitted to the NICU due to pyriform aperture stenosis. Craniofacial abnormalities, intracranial calcification, osteosclerosis, chondrodysplasia punctata, and a mutation of FAM20C was identified. She was subsequently discharged without surgical intervention and is now 2 years old with mild neurodevelopmental delays. Images of cerebral hyperechogenicity by fetal ultrasonography in a non-lethal case were described herein for the first time. This patient represents a rare occurrence of a child with Raine syndrome born to Japanese parents and confirms that this syndrome is not always lethal. Even if Raine syndrome is suspected in a fetus due to cerebral hyperechogenicity and a hypoplastic nose, cerebral hyperechogenicity without pulmonary hypoplasia does not always predict lethality or severe neurodevelopmental delays. The information provided herein will be useful for prenatal counseling.

Structural abnormality of substantia nigra induced by methamphetamine abuse.

BACKGROUND: Methamphetamine abuse has been linked to an increased risk of Parkinson's disease. OBJECTIVE: The objective of this study was to investigate structural abnormality of the substantia nigra in past methamphetamine users using transcranial sonography. METHODS: In a cross-sectional, observational study, echogenicity of the substantia nigra was assessed in 59 past methamphetamine users and 59 matched controls. The frequencies of an abnormal spatial extension of the substantia nigra as well as the average sizes of left and right substantia nigra were evaluated. RESULTS: The average echogenic size of the substantia nigra was larger in methamphetamine users (0.22 ± 0.06 cm2 ) when compared with controls (0.17 ± 0.05 cm2 , P < .001). Furthermore, the frequency of enlarged, echogenic substantia nigra was increased in methamphetamine users (42% vs 12% in controls, P < .001). Partial correlation analysis revealed an association of echogenic substantia nigra size with estimated total lifetime intake of methamphetamine (r55 = 0.395, P = .002). CONCLUSIONS: Current data link methamphetamine abuse in humans to injury of substantia nigra neurons and an increased risk of Parkinson's disease. © 2017 International Parkinson and Movement Disorder Society.

Transcranial sonography in dopa-responsive dystonia.

BACKGROUND AND PURPOSE: Mutations in the GCH1 gene, encoding GTP cyclohydrolase 1, the enzyme critically important for dopamine production in nigrostriatal neurons, are the most common cause of dopa-responsive dystonia (DRD), characterized predominantly by limb dystonia, although parkinsonian features may also be present. It has been suggested that DRD is a neurochemical rather than neurodegenerative disorder. METHODS: Transcranial brain sonography, which might be a risk marker for nigral injury, was obtained from 141 subjects divided into four groups: (i) 11 patients with genetically confirmed DRD; (ii) 55 consecutive patients with Parkinson's disease (PD); (iii) 30 patients diagnosed as isolated adult-onset focal dystonia; and (iv) 45 healthy controls (HCs). RESULTS: Substantia nigra hyperechogenicity was present in 63.6% of patients with DRD, which was significantly different in comparison to patients with dystonia (20%) and HCs (6.7%), but not in comparison to the PD group (87.3%). Also, values of the maximal areas of substantia nigra hyperechogenicity in patients with DRD were higher in comparison to HCs, but significantly lower than among the PD group. CONCLUSIONS: We suggested that the observed transcranial brain sonography features in patients with DRD might primarily be risk markers for particular clinical features (parkinsonism, dystonia) occurring in the specific genetic context (i.e. GCH1 mutations), or might reflect compensated neurodegenerative processes triggered by the long-lasting dopamine deficiency due to the profound delay in levodopa treatment in our patients with DRD.

Transcranial sonography image characteristics in different Parkinson's disease subtypes.

Recently, Parkinson's disease (PD) has been classified into three subtypes: postural instability gait difficulty (PIGD), tremor dominate (TD), and indeterminate PD. Transcranial sonography (TCS) is considered to be an important tool to diagnose PD. However, it is uncertain that whether there are differences in TCS image characteristics in different PD subtypes, so 373 idiopathic PD (188 PIGD, 108 TD, 77 indeterminate PD) were registered and received TCS in our investigation; also, the association between clinical characteristics and TCS results in different PD subtypes was analyzed. In accordance with several previous studies, we detected substantia nigra (SN) by TCS in 85.4% of patients with idiopathic PD; we concluded that PIGD patients had more serious disease than TD and indeterminate PD group (p < 0.05). They always had larger SN hyperechogenicity areas on TCS (p < 0.05), and we found that there was no correlation between SN hyperechogenicity and disease duration or severity (p > 0.05). Similarly, abnormal brainstem raphe signal was also more often in PIGD group than in TD and indeterminate PD group (p < 0.05), which might imply that PIGD group was vulnerable to suffer from depression in the future.

Substantia nigra hyperechogenicity and Parkinson's disease risk in patients with essential tremor.

BACKGROUND: Several studies have reported an increased risk for patients with essential tremor to develop Parkinson's disease. In addition, hyperechogenicity in the area of the substantia nigra has been associated with a markedly increased risk for Parkinson's disease. The objective of this study was to evaluate the validity of substantia nigra hyperechogenicity in patients with essential tremor as a risk marker for Parkinson's disease. METHODS: Transcranial sonography was performed in 70 patients suffering from essential tremor. Fifty-four of these patients were available for follow-up after a mean of 6.16 ± 2.05 years and were assessed for the incidence of new-onset Parkinson's disease. RESULTS: The relative risk for developing Parkinson's disease in patients with essential tremor who had hyperechogenicity at baseline versus those without this hyperechogenicity was 7.00 (95% confidence interval, 1.62-30.34; sensitivity, 77.8%; specificity, 75.6%). CONCLUSIONS: Substantia nigra hyperechogenicity is also associated with an increased risk for Parkinson's disease in patients with essential tremor. These findings further support the potential role of this echofeature as a risk marker for Parkinson's disease.

Substantia nigra hyperechogenicity is related to decline in verbal memory in healthy elderly adults.

BACKGROUND AND PURPOSE: Deficits in cognition have been reported in Parkinson's disease (PD) already in the early and even in the pre-motor stages. Whilst substantia nigra hyperechogenicity measured by transcranial B-mode sonography (TCS) represents a strong PD marker and is associated with an increased risk for PD in still healthy individuals, its association with cognitive performance in prodromal PD stages is not well established. METHODS: Two different cohorts of healthy elderly individuals were assessed by TCS and two different neuropsychological test batteries covering executive functions, verbal memory, language, visuo-constructional function and attention. Cognitive performance was compared between individuals with hyperechogenicity (SN+) and without hyperechogenicity (SN-). RESULTS: In both cohorts, SN+ individuals performed significantly worse than the SN- group in tests assessing verbal memory (word list delayed recall P = 0.05, logical memory II P < 0.017). Significant differences in Mini-Mental State Examination score (cohort 1, P = 0.02) and executive function tests (cohort 2, Stroop Color-Word Reading, P = 0.004) could only be shown in one of the two cohorts. No between-group effects were found in other cognitive tests and domains. CONCLUSIONS: These results indicate that individuals with the PD risk marker SN+ perform worse in verbal memory compared to SN- independent of the assessment battery. Memory performance should be assessed in detail in individuals at risk for PD.

Substantia Nigra Hyperechogenicity: Validation of Transcranial Sonography for Parkinson Disease Diagnosis in a Large Estonian Cohort.

OBJECTIVES: Substantia nigra hyperechogenicity is a promising biomarker for Parkinson disease (PD). Substantia nigra hyperechogenicity has previously been established as a useful diagnostic criterion in several European and Asian patient cohorts. However, diagnostic cutoff values for substantia nigra hyperechogenicity remain unknown for most patient populations. This study validated the diagnostic accuracy of substantia nigra hyperechogenicity in a large cohort of patients with PD in Estonia. METHODS: The study included 300 patients with PD from Estonia, representing 10% of the national PD patient population, and 200 healthy control participants. To define the optimal cutoff value in the PD cohort, data from a single assessment versus repetitive assessments by transcranial sonography were compared. With the use of 3 repetitive assessments, the diagnostic accuracy of the data was measured. In addition, calculations for percentile values were used to define substantia nigra hyperechogenicity among controls. RESULTS: Our data showed that the multiassessment approach yielded higher diagnostic accuracy than a single assessment (P = .021). The highest diagnostic accuracy was achieved by using the measurement mean to define substantia nigra hyperechogenicity, which was 0.23 cm(2) (sensitivity, 88.7%; specificity, 92.2%), whereas single measurements detected PD with higher sensitivity (sensitivity, 93.2%; specificity, 85.1%). No significant difference was found between mean and median measurements (P= .18). CONCLUSIONS: This study indicates the diagnostic merit of transcranial sonography in PD diagnosis in an additional population and demonstrates that transcranial sonography of the substantia nigra is a relevant and useful diagnostic tool for patients with PD.

A population-based study on combined markers for early Parkinson's disease.

The prerequisite for an earlier diagnosis of Parkinson's disease (PD) are markers that are both sensitive and specific for clinically definite PD and its prediagnosic phases. Promising candidates include enlarged hyperechogenicity of the substantia nigra (SN+) on transcranial sonography (TCS) and hyposmia. However, despite good sensitivity and specificity, both markers have yet failed to yield reliable predictions. We pursue the possibility of combined use in an ongoing population-based cohort. Subjects were recruited from 10,000 inhabitants of Luebeck/Germany aged 50 to 79 years and additional PD patients from our outpatient clinic. After neurological examination, 715 subjects were grouped into clinically definite PD (n = 106), possible prediagnostic PD (ppPD; n = 73), and a control group subdivided into healthy individuals (n = 283) and controls with diseases other than PD (n = 253). Subjects underwent TCS and smell testing. Sensitivity and specificity of SN+ and hyposmia were good for PD; however, positive predictive values (PPV) of both SN+ (5.2%) and olfaction (2.5%) were low. At least one positive/both positive markers were present in 33%/1% of healthy controls, 33%/2% of diseased controls, 62%/7% of ppPD, and 94%/51% of PD. When combining SN+ and hyposmia, PPV increased to 17.6%, with a sensitivity of 51% and a specificity of 98%. Both SN+ and hyposmia offer good enrichment towards PD and ppPD, are stable against other diseases, and the combination of markers highly increases specificity. However, if the combination of SN+ and hyposmia were used as criterion for PD diagnosis, almost half of clinically definite PD and more than 90% of ppPD would have been missed.

Light pigmentation phenotype is correlated with increased substantia nigra echogenicity.

OBJECTIVE: This study was undertaken to address the question of whether pigmentation may be mechanistically linked with Parkinson's disease. METHODS: In a cross-sectional, observational study, 116 healthy subjects received transcranial sonography of the substantia nigra. Pigmentation phenotype was assessed using the Fitzpatrick skin phototype classification, and five additional phenotypic pigmentation traits as well as a photographic method (Melanin index) in a subgroup of 46 subjects. RESULTS: Lighter skin phototype was associated with larger echogenic substantia nigra area and increased prevalence of abnormally enlarged echogenic substantia nigra area. The strongest association of substantia nigra echogenicity and phenotypic pigmentation traits was found for hair color and facial tanning. INTERPRETATION: Findings suggest an increasing prevalence of structural abnormality of substantia nigra with decreasing darkness of skin and thus may provide additional evidence in favor of a pathogenic link of pigmentation and Parkinson's disease.

Ultrasonographic hyperechoic lesions of the breast: are they always benign?

BACKGROUND: Most of the breast lesions show hypoechogenicity relative to fat on ultrasonography. The frequency and malignancy rate of hyperechoic lesions are not investigated in a large series. PURPOSE: To evaluate the frequency and malignancy rate of hyperechoic lesions on breast sonography and to investigate sonographic characteristics that may predict malignancy in hyperechoic breast lesions. MATERIAL AND METHODS: Radiologic reports of 16,416 patients who underwent breast sonography between 2007 and 2008 were searched using "hyperechoic", "echogenic" or "heterogeneous echoic" to describe lesions. Sonographic findings were evaluated according to the Breast Imaging Reporting and Data System lexicon. Clinical records including follow-up and pathologic findings were also reviewed. We calculated the frequency of hyperechoic lesions and their malignancy rate. Differences in sonographic appearances between benign and malignant lesions were also investigated. RESULTS: Among the 16,416 patients, 103 (0.6%) hyperechoic lesions were identified (mean size, 1.79 cm). Of these 103 lesions, 27 (26.2%) were pathologically evaluated and five (4.9%, 4 invasive ductal carcinoma and 1 mucinous carcinoma) were confirmed as malignant. Among the 819 malignant lesions diagnosed using sonography-guided core needle biopsy, five (0.6%) were hyperechoic. In benign lesions, fat necrosis and fibroadenoma were common pathologic diagnoses. Malignant lesions were more likely to have irregular shape (P = 0.003), non-parallel orientation (P = 0.002), non-circumscribed margin (P = 0.007), and a hypoechoic area (P = 0.027) than benign lesions. All hyperechoic carcinomas were seen as suspicious masses on mammograms. CONCLUSION: Hyperechoic masses are very rare and mostly benign. As an adjunct to mammography, the imaging findings reported here could help to avoid misdiagnosis for malignant hyperechoic lesion.

Diagnostic value of combined assessment of olfaction and sustantia nigra hyperechogenicity for Parkinson's disease.

INTRODUCTION: Hyposmia and substantia nigra hyperechogenicity (SN+) are characteristic markers of Parkinson's disease (PD), although their diagnostic value in isolation may be limited. We evaluated the combined prevalence of both disorders in patients diagnosed with PD and assessed their diagnostic yield compared to a sample with essential tremor (ET) and another group of healthy subjects. METHODS: Patients diagnosed with PD and ET and treated in our outpatient clinic were enrolled. Olfaction was assessed using the "Sniffin' Sticks" odour identification test (SS-12) and hyperechogenicity of the substantia nigra (SN+) was assessed by transcranial duplex ultrasound. RESULTS: A total of 98 subjects were analysed, comprising 30 with PD, 21 with ET, and 47 controls. The respective prevalence rates of hyposmia (SS-12 < 8) and SN+ (area > .24cm(2)) were 70% and 83.3% in PD, 33.3% and 9.5% in ET, and 17% and 10.6% in controls. Both markers were present in 63% of patients with PD, none of the patients with ET, and only 2 of the controls. CONCLUSIONS: Combined use of substantia nigra sonography and olfactory testing with SS-12, two rapid, safe, and accessible tests, was more specific than each isolated marker for distinguishing patients with PD from patients with ET and control subjects. Since both markers have been described in very early phases of PD, combined use may be helpful in providing early diagnosis of PD.

Advancements in understanding substantia nigra hyperechogenicity via transcranial sonography in Parkinson's disease and its clinical implications.

Amidst rising Parkinson's disease (PD) incidence in an aging global population, the need for non-invasive and reliable diagnostic methods is increasingly critical. This review evaluates the strategic role of transcranial sonography (TCS) in the early detection and monitoring of PD. TCS's ability to detect substantia nigra hyperechogenicity offers profound insights into its correlation with essential neuropathological alterations-namely, iron accumulation, neuromelanin depletion, and glial proliferation-fundamental to PD's pathophysiology. Our analysis highlights TCS's advantages, including its non-invasiveness, cost-effectiveness, and ease of use, positioning it as an invaluable tool for early diagnosis and continual disease progression monitoring. Moreover, TCS assists in identifying potential risk and protective factors, facilitating tailored therapeutic strategies to enhance clinical outcomes. This review advocates expanding TCS utilization and further research to maximize its diagnostic and prognostic potential in PD management, contributing to a more nuanced understanding of the disease.

Transcranial Sonography Characteristics of Cerebellar Neurodegenerative Ataxias.

Cerebellar neurodegenerative ataxias are a group of disorders affecting the cerebellum and its pathways with different neurological structures. Transcranial sonography (TCS) has been used for the evaluation of brain parenchymal structures in various diseases because of its fast and safe utilization, especially in neuropsychiatric and neurodegenerative diseases. The aim of our study was to investigate TCS characteristics of patients with neurodegenerative cerebellar ataxias. In our study, we included 74 patients with cerebellar degenerative ataxia; 36.5% had autosomal dominant onset, while 33.8% had sporadic onset. Standardized ultrasonographic planes were used for the identification of brain structures of interest. The SARA, INAS, neuropsychological and psychiatric scales were used for the further clinical evaluation of our study participants. The brainstem raphe was discontinued in 33.8% of the patients. The substantia nigra (SN) hyperechogenicity was identified in 79.7%. The third and fourth ventricle enlargement had 79.7% and 45.9% of patients, respectively. A positive and statistically significant correlation was found between SN hyperechogenicity with dystonia (p < 0.01), rigidity and dyskinesia (p < 0.05). The higher SARA total score is statistically significantly correlated with the larger diameter of the III (r = 0.373; p = 0.001) and IV ventricles (r = 0.324; p = 0.005). In such patients, the echogenicity of substantia nigra has been linked to extrapyramidal signs, and raphe discontinuity to depression. Furthermore, ataxia and its clinical subtypes have positively correlated with the IV ventricle diameter, indicating brain atrophy and brain mass reduction.

Hyperimmunoglobulin for prevention of congenital cytomegalovirus disease.

Primary cytomegalovirus (CMV) infection during the first half of pregnancy is responsible for the majority of symptomatic congenital infections. Between one-third and one-half of fetuses become infected, and up to one-half of infected fetuses will have neurologic or sensorineural sequelae at birth or later in life. Following favorable results obtained in animal experiments, observational studies have shown beneficial effects after administration of high-titer CMV hyperimmunoglobulin to pregnant women with fetal infection or disease subsequent to primary CMV infection. The mechanisms of action of hyperimmunoglobulin are multiple and not yet fully understood. However, they could reside in 2 major properties: (1) antiviral activities due to high-avidity neutralizing antibodies and (2) immunomodulating activities mostly including downregulation of cytokine-mediated cellular immune responses. A decreased viral pathogenicity occurs as an immediate consequence, whereas reduced placental inflammation and restored function are the long-term effects.

Quantitative Transcranial Sonography Evaluation of Substantia Nigra Hyperechogenicity Is Useful for Predicting Levodopa-Induced Dyskinesia in Parkinson Disease.

Levodopa-induced dyskinesia (LID) is a common motor complication in Parkinson disease (PD). Abnormal substantia nigra hyperechogenicity (SN+), detected by transcranial sonography (TCS), plays an important role in the differential diagnosis of PD. The purpose of this study was to investigate the predictive performance of quantitative SN+ evaluations for LID. Five hundred sixty-two individuals were included in our analysis, and 198 individuals were followed up. These individuals were divided into two groups at baseline: the PD with LID (PD+LID) group and the PD without LID (PD-LID) group. The association between total hyperechogenic area of the SN on both sides (SNT) and LID was analyzed by binary logistic analysis. A binary logistic regression model including SNT was applied to establish a model for discriminating LID. At baseline, 105 (18.7%) individuals were diagnosed with LID. The PD+LID group had a longer disease duration, shorter education duration, higher levodopa equivalent doses, greater disease severity and larger SNT. A model combining clinical features and SNT was further established with better efficiency (area under the receiver operating characteristic curve = 0.839). One hundred ninety-eight individuals were followed up; individuals with a larger SNT and a higher predicted probability were more likely to develop LID in our follow-up. Our study determined that quantitative TCS evaluation of SN echogenicity is useful in predicting LID in PD.