Substantia Nigra Hyperechogenicity Research Articles

Usefulness of Cardiac MIBG Scintigraphy, Olfactory Testing and Substantia Nigra Hyperechogenicity as Additional Diagnostic Markers for Distinguishing between Parkinson's Disease and Atypical Parkinsonian Syndromes.

BackgroundWe aimed to evaluate the utility of the combined use of cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphy, olfactory testing, and substantia nigra (SN) hyperechogenicity on transcranial sonography (TCS) in differentiating Parkinson’s disease (PD) from atypical parkinsonian syndromes (APSs), such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP).MethodsCardiac MIBG scintigraphy, card-type odor identification testing (Open Essence (OE), Wako, Japan), and TCS were performed with 101 patients with PD and 38 patients with APSs (MSA and PSP). Receiver operating characteristic (ROC) curve analysis was used to assess the sensitivity and specificity of these batteries for diagnosing PD from APSs. The diagnostic accuracy of the three tests was also assessed among patients at the early disease stage (drug-naïve patients with a disease duration of 3 years or less).ResultsIn differentiating PD from APSs, the area under the ROC curve was 0.74 (95% CI, 0.65–0.83), 0.8 (95% CI, 0.73–0.87), and 0.75 (95% CI, 0.67–0.82) for TCS, cardiac MIBG scintigraphy, and olfactory testing, respectively. The diagnostic sensitivity and specificity were 53.1% and 91.7%, respectively, for TCS, 70.3% and 86.8%, respectively, for cardiac MIBG scintigraphy, 58.4% and 76.3%, respectively, for OE. Among early-stage patients, sensitivity and specificity were 50.0% and 93.8%, respectively, for TCS, 57.1% and 87.5%, respectively, for cardiac MIBG scintigraphy, and 54.8% and 79.2%, respectively, for OE. At least one positive result from 3 tests improved sensitivity (86.1%) but decreased specificity (63.2%). In contrast, at least 2 positive results from 3 tests had good discrimination for both early-stage patients (50.0% sensitivity and 93.8% specificity) and patients overall (57.8% sensitivity and 95.8% specificity). Positive results for all 3 tests yielded 100% specificity but low sensitivity (25%).ConclusionsAt least 2 positive results from among TCS, cardiac MIBG scintigraphy, and olfactory testing can support clinical diagnosis in distinguishing PD from APSs.

Transcranial sonography in dopa-responsive dystonia.

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. 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). 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. 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.

Use of Gray-Level Histograms to Assess Substantia Nigra Echogenicity in Transcranial Sonography Images of Parkinson Disease Patients

A substantial body of research has shown that Parkinson disease (PD) patients display an enlarged hyperechogenic substantia nigra (SN) by transcranial sonography (TCS). Nonetheless, the categorization of SN echogenicity is still subjective. A method is described to quantify SN echogenicity based on the gray-level histograms of digitized TCS images. In 31 PD patients and 57 controls, the gray-scale mean (GSM) of the SN, mesencephalon, and basal cisterns and their ratios were assessed using image-editing computer software. The GSM values were compared between the groups and correlated with age, SN area, and disease duration. The SN GSM was significantly higher in the PD group ( P < .05) with a positive correlation with age but not with disease duration. In this cohort of participants, mesencephalon echogenicity was found to increase with disease duration. These results would suggest quantitatively SN hyperechogenicity in PD. Quantifying SN echogenicity is feasible and might minimize subjectivity in PD diagnosis by TCS. The method has the potential to disclose subtle changes in other midbrain structures’ echogenicity engendered by the disease process as well.

Standards in neurosonology. Part III

The paper presents standards related to ultrasound imaging of the cerebral vasculature and structures. The aim of this paper is to standardize both the performance and description of ultrasound imaging of the extracranial and intracranial cerebral arteries as well as a study of a specific brain structure, i.e. substantia nigra hyperechogenicity. The following aspects are included in the description of standards for each ultrasonographic method: equipment requirements, patient preparation, study technique and documentation as well as the required elements of ultrasound description. Practical criteria for the diagnosis of certain pathologies in accordance with the latest literature were also presented. Furthermore, additional comments were included in some of the sections. Part I discusses standards for the performance, documentation and description of different ultrasound methods (Duplex, Doppler). Part II and III are devoted to standards for specific clinical situations (vasospasm, monitoring after the acute stage of stroke, detection of a right-to-left shunts, confirmation of the arrest of the cerebral circulation, an assessment of the functional efficiency of circle of Willis, an assessment of the cerebrovascular vasomotor reserve as well as the measurement of substantia nigra hyperechogenicity).

Transcranial sonography findings related to depression in parkinsonian disorders: cross-sectional study in 126 patients.

Background. Transcranial sonography (TCS) has emerged as a potential diagnostic tool for Parkinson’s disease. Recent research has suggested that abnormal echogenicity of substantia nigra, raphe nuclei and third ventricle is associated with increased risk of depression among these patients. We sought to reproduce these findings in an ongoing larger study of patients with parkinsonian syndromes.Methods. A total of 126 patients with parkinsonian symptoms underwent the Hamilton Depression Scale, and TCS of the substantia nigra (SN) (n = 126), the raphe nuclei (RN) (n = 80) and the third ventricle (n = 57). We then calculated the correlation between depression and hyper-echogenic SN, hypo-echogenic RN and a wider third ventricle.Results. In patients with PD we found no significant difference of the SN between non-depressed and depressed patients (46% vs. 22%; p = 0.18). Non-depressed patients with other parkinsonisms more often had hyperechogenicity of the SN than depressed patients (51% vs. 0%; p = 0.01). We found no relation between depression and the echogenicity of the RN or the width of the third ventricle.Conclusions. In patients with parkinsonian syndromes, we found no association between depression and hyper-echogenic SN, hypo-echogenic RN or a wider third ventricle, as determined by transcranial sonography.

Accuracy of transcranial brain parenchyma sonography in the diagnosis of dementia with Lewy bodies.

Transcranial sonography (TCS) of the brain parenchyma is used to visualize alterations in the substantia nigra (SN) and it is applied for early diagnosis of Parkinson's disease. Our aim was to explore specific echogenic alterations of the SN in dementia with Lewy bodies (DLB) compared to Alzheimer's disease (AD). Seventy-one subjects underwent TCS: 22 DLB, 28 AD and 21 healthy elderly controls. Cognitive impairment, extrapyramidal signs, visual hallucinations, fluctuations and rapid eye movement sleep behaviour symptoms were investigated. TCS assessed SN hyperechogenicity and symmetry. Transcranial sonography revealed SN hyperechogenicity in 100% of DLB compared to 50% of AD and 30% of controls. Mean SN echogenic area (cm(2) ) was 0.22 ± 0.03 in DLB, 0.15 ± 0.03 in AD and 0.14 ± 0.03 in controls (P < 0.0001). More than 50% of DLB presented a marked hyperechogenicity (cutoff value >0.22 cm(2) ) compared to only 10% of AD (P < 0.0003). DLB had symmetrical SN enlargement, whereas AD were mostly asymmetrical (P = 0.015). A combination of SN echogenic area and asymmetry index had a sensitivity of 88.9% and a specificity of 81.2% in discriminating DLB from AD (positive predictive value 85.7%, negative predictive value 85.7%). No association was found between SN hyperechogenicity and Unified Parkinson's Disease Rating Scale part III, Mini Mental State Examination or the presence of visual hallucinations. Transcranial sonography may be a valid supportive tool in the diagnostic workup of neurodegenerative dementia helping clinicians to distinguish DLB from AD even at the early stages.

Comparison of transcranial sonography-magnetic resonance fusion imaging in Wilson's and early-onset Parkinson's diseases

IntroductionWilson's disease (WD) is a hereditary disorder caused by ATP7B mutations resulting in systemic copper accumulation. WD may manifest as early-adulthood parkinsonism; and atypical cases may be difficult to distinguish from early-onset Parkinson's disease (EO-PD), a neurodegenerative disorder with onset ≤40 years of age. The aim of our study was to compare transcranial sonography (TCS)–magnetic resonance fusion imaging in WD and EO-PD and examine whether TCS can provide clinically useful information. MethodsWe examined 22 WD, 16 EO-PD, and 24 healthy control subjects. We measured echogenicity and determined presence of MRI signal changes in T2-weighted images in the substantia nigra (SN) and lentiform nucleus (NL). TCS with the capability of magnetic resonance fusion and Virtual Navigator was used. The echogenicity indices of SN and NL were processed using digital image analysis to eliminate subjective evaluation errors. ResultsMean SN echogenicity index in EO-PD (39.8 ± 5.9 [SD]) was higher compared to WD (28.0 ± 4.6, p < 0.0001) and control subjects (28.8 ± 4.9, p < 0.0001). Mean NL echogenicity index was higher in WD (117.5 ± 37.0) compared to EO-PD (61.6 ± 5.4, p < 0.0001) and control subjects (54.9 ± 11.2, p < 0.0001). The SN hyperechogenicity had sensitivity 93.8%, and specificity 90.9%, while the NL hyperechogenicity had sensitivity 95.5% and specificity 93.8% for differentiation of WD and EO-PD. NL hyperechogenicity was more pronounced in WD subjects with putaminal MRI T2 hyperintensity (p < 0.05) but was also present in subjects without MRI abnormality. ConclusionsThere are distinct TCS findings in WD and EO-PD complementary to MRI that can be utilized as highly sensitive and specific biomarkers of these disorders.

Study on transcranial sonography in patients with idiopathic rapid eye movement sleep behavior disorder

Objective To investigate the changes of transcranial sonography (TCS) in patients with rapid eye movement sleep behavior disorder (RBD). Methods Fifteen patients fulfilled the diagnostic criteria of RBD according to International Classification of Sleep Disorders (ICSD, 2nd edition). Under the monitor of polysomnography (PSG), the sleep architectures of all RBD cases were evaluated by Polysmith software and visual analysis. Furthermore, all RBD patients and 15 normal controls underwent TCS. Cases with substantia nigra echo intensity over Ⅲ grade and substantia nigra area over 0.20 cm 2 were supposed to be hyperechogenicity. Additionally, the width of the third ventricle was measured and whether there was hyperechogenicity in basal ganglia was evaluated. The cognitive functions were evaluated by Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Results RBD patients presented typical clinical manifestations and electrophysiologic changes. No significant difference ( P = 0.080, 0.109) was found in the comparison of hyperechogenicity rate on substantia nigra (6/15) and basal ganglia (7/15) in RBD patients and normal controls (1/15, 2/15). No significant difference in the comparison of MoCA was found in RBD patients with or without substantia nigra hyperechogenicity ( P = 0.075). The RBD patients with hyperechogenicity on basal ganglia had higher MMSE scores than those without hyperechogenicity on basal ganglia, and the difference was significant ( P = 0.021). Conclusions RBD which is suggested as the prodromal period of synucleinopathy may present hyperechogenicity in substantia nigra and basal ganglia on TCS. TCS could detect subclinical changes of brain and evaluate the risk of synucleinopathy. DOI: 10.3969/j.issn.1672-6731.2016.04.010

Sonographic Alteration of Basal Ganglia in Different Forms of Primary Focal Dystonia: A Cross-sectional Study.

Background:Few studies have addressed whether abnormalities in the lenticular nucleus (LN) are characteristic transcranial sonography (TCS) echo features in patients with primary dystonia. This study aimed to explore alterations in the basal ganglia in different forms of primary focal dystonia.Methods:cross-sectional observational study was performed between December 2013 and December 2014 in 80 patients with different forms of primary focal dystonia and 55 neurologically normal control subjects. TCS was performed in patients and control subjects. Multiple comparisons of multiple rates were used to compare LN hyperechogenicity ratios between control and patient groups.Results:Thirteen individuals were excluded due to poor temporal bone windows, and two subjects were excluded due to disagreement in evaluation by sonologists. Totally, 70 patients (cervical dystonia, n = 30; blepharospasm, n = 30; oromandibular dystonia, n = 10) and 50 normal controls were included in the final analysis. LN hyperechogenicity was observed in 51% (36/70) of patients with primary focal dystonia, compared with 12% (6/50) of controls (P < 0.001). Substantia nigra hyperechogenicity did not differ between the two groups. LN hyperechogenicity was observed in 73% (22/30) of patients with cervical dystonia, a greater prevalence than in patients with blepharospasm (33%, 10/30, P = 0.002) and oromandibular dystonia (40%, 4/10, P = 0.126). LN hyperechogenicity was more frequently observed in patients with cervical dystonia compared with controls (73% vs. 12%, P < 0.001); however, no significant difference was detected in patients with blepharospasm (33% vs. 12%, P = 0.021) or oromandibular dystonia (40% vs. 12%, P = 0.088).Conclusions:LN hyperechogenicity is more frequently observed in patients with primary focal dystonia than in controls. It does not appear to be a characteristic TCS echo feature in patients with blepharospasm or oromandibular dystonia.

Substantia nigra hyperechogenicity does not correlate with motor features in Parkinson's disease

IntroductionThe evaluation of hyperechogenicity of the substantia nigra (SN) by transcranial sonography (TCS) is validated for the diagnosis of Parkinson's disease (PD). However, its correlation with the severity of motor involvement is still uncertain. MethodsWe included patients with clinical diagnosis of idiopathic PD in a cross-sectional study. All patients were evaluated with Unified Parkinson's Disease Rating Scale-motor score (UPDRS-III) and TCS at the same day with measurement of the area of SN hyperechogenicity for each side. We analysed the association between the area of SN hyperechogenicity and the contralateral motor scores of UPDRS-III, adjusting for age and dominance of the patient (statistical significance set to p<0.05). Results35 patients were analysed, 3 (8.6%) were excluded due to poor temporal acoustic bone window.From a total of 32 patients, the mean age was 58.4 (±11.2)years. The mean area of SN hyperechogenicity was: right 0.26 (±0.12)cm2 and left 0.27 (±0.07)cm2. The mean score of UPDRS-III was 18.9 (±6.1). There were no statistically significant association between the scores of the UPDRS-III (rigidity, tremor and bradykinesia) and the contralateral area of SN hyperechogenicity. ConclusionThe area of SN hyperechogenicity did not correlate with motor deterioration in Parkinson's disease.

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

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. 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-). 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. 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.

Adults with a history of illicit amphetamine use exhibit abnormal substantia nigra morphology and parkinsonism

IntroductionThe sonographic appearance of the substantia nigra is abnormally bright and enlarged (hyperechogenic) in young adults with a history of illicit stimulant use. The abnormality is a risk factor for Parkinson's disease. The aim of the current study was to identify the type of illicit stimulant drug associated with substantia nigra hyperechogenicity and to determine if individuals with a history of illicit stimulant use exhibit clinical signs of parkinsonism. We hypothesised that use of amphetamines (primarily methamphetamine) is associated with substantia nigra hyperechogenicity and clinical signs of parkinsonism. MethodsThe area of echogenic signal in the substantia nigra was measured in abstinent human amphetamine users (n = 27; 33 ± 8 years) and in three control groups comprising a) ‘ecstasy’ users (n = 19; 23 ± 3 years), b) cannabis users (n = 30; 26 ± 8 years), and c) non-drug users (n = 37; 25 ± 7 years). A subset of subjects (n = 55) also underwent a neurological examination comprising the third and fifth part of the Unified Parkinson's Disease Rating Scale. ResultsArea of substantia nigra echogenicity was significantly larger in the amphetamine group (0.276 ± 0.080 cm2) than in the control groups (0.200 ± 0.075, 0.190 ± 0.049, 0.191 ± 0.055 cm2, respectively; P < 0.002). The score on the clinical rating scale was also significantly higher in the amphetamine group (8.4 ± 8.1) than in pooled controls (3.3 ± 2.8; P = 0.002). ConclusionIllicit use of amphetamines is associated with abnormal substantia nigra morphology and subtle clinical signs of parkinsonism. The results support epidemiological findings linking use of amphetamines, particularly methamphetamine, with increased risk of developing Parkinson's disease later in life.

Standards in neurosonology. Part II.

The paper presents standards related to ultrasound imaging of the cerebral vasculature and structures. The aim of this paper is to standardize both the performance and description of ultrasound imaging of the extracranial and intracranial cerebral arteries as well as a study of a specific brain structure, i.e. substantia nigra hyperechogenicity. The following aspects are included in the description of standards for each ultrasonographic method: equipment requirements, patient preparation, study technique and documentation as well as the required elements of ultrasound description. Practical criteria for the diagnosis of certain pathologies in accordance with the latest literature were also presented. Furthermore, additional comments were included in some of the sections. Part I discusses standards for the performance, documentation and description of different ultrasound methods (Duplex, Doppler). Part II and III are devoted to standards for specific clinical situations (vasospasm, monitoring after the acute stage of stroke, detection of a right-to-left shunts, confirmation of the arrest of the cerebral circulation, an assessment of the functional efficiency of circle of Willis, an assessment of the cerebrovascular vasomotor reserve as well as the measurement of substantia nigra hyperechogenicity).

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

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. 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. 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%). 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.

Diagnostic Accuracy of Transcranial Sonography of the Substantia Nigra in Parkinson's disease: A Systematic Review and Meta-analysis.

A large number of articles have reported substantia nigra hyperechogenicity in Parkinson’s disease (PD) and have assessed the diagnostic accuracy of transcranial sonography (TCS); however, the conclusions are discrepant. Consequently, this systematic review and meta-analysis aims to consolidate the available observational studies and provide a comprehensive evaluation of the clinical utility of TCS in PD. Totally, 31 studies containing 4,386 participants from 13 countries were included. A random effects model was utilized to pool the effect sizes. Meta-regression and sensitivity analysis were performed to explore potential heterogeneity. Overall diagnostic accuracy of TCS in differentiating PD from normal controls was quite high, with a pooled sensitivity of 0.83 (95% CI: 0.81–0.85) and a pooled specificity of 0.87 (95% CI: 0.85–0.88). The positive likelihood ratio, the negative likelihood ratio and diagnostic odds ratio were calculated 6.94 (95% CI: 5.09–9.48), 0.19 (95% CI: 0.16–0.23), and 42.89 (95% CI: 30.03–61.25) respectively. Our systematic review of the literature and meta-analysis suggest that TCS has high diagnostic accuracy in the diagnosis of PD when compared to healthy control.

Substantia nigra echogenicity correlated with clinical features of Parkinson's disease

BackgroundTranscranial sonography can display structural alterations in the substantia nigra (SN) of patients with Parkinson's disease (PD), and is considered to be a potential useful tool for the diagnosis of PD. The aim of this study was to assess the correlation between SN echogenicity and clinical features in Chinese patients with PD. MethodsA total of 420 subjects including 290 patients with PD and 130 controls were recruited from the neurological clinic or the community. Transcranial sonographic evaluations of the SN were performed in all subjects, and motor and non-motor symptoms were thoroughly assessed by a series of rating scales in PD patients. ResultsTwo hundred and one patients were successfully assessed by transcranial sonography. SN hyperechogenicity was found to be associated with male sex (p = 0.004), higher scores on the Unified Parkinson's Disease Rating Scale (UPDRS) part II (p = 0.001) and autonomic symptoms scores (p = 0.003). Moreover, regression analysis revealed that UPDRS part II scores (odds ratio = 1.141, p < 0.001) and gender (odds ratio = 2.409, p = 0.007) could be the independent predictors for SN hyperechogenicity; in addition, among all items of UPDRS part II, speech, dressing, hygiene, and turning in bed and adjusting bed clothes significantly correlated with SN hyperechogenicity. ConclusionsThis is the first report suggesting the correlation between SN echogenicity and UPDRS part II, and we conclude that increased SN echogenicity might reflect more severe disease disability or poorer medical response.

Long-Term Follow-up Investigation of Isolated Rapid Eye Movement Sleep Without Atonia Without Rapid Eye Movement Sleep Behavior Disorder: A Pilot Study.

Idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) is a harbinger of synuclein-mediated neurodegenerative diseases. It is unknown if this also applies to isolated REM sleep without atonia (RWA). We performed a long-term follow-up investigation of subjects with isolated RWA. Participants were recruited from 50 subjects with isolated RWA who were identified at the sleep laboratory of the Department of Neurology at the Medical University of Innsbruck between 2003 and 2005. Eligible subjects underwent follow-up clinical examination, polysomnography, and assessment of neurodegenerative biomarkers (cognitive impairment, finger speed deficit, impaired color vision, olfactory dysfunction, orthostatic hypotension, and substantia nigra hyperechogenicity). After a mean of 8.6 ± 0.9 y, 1 of 14 participating subjects (7.3%) progressed to RBD. Ten of 14 RWA subjects (71.4%) were positive for at least one neurodegenerative biomarker. Substantia nigra hyperechogenicity and presence of mild cognitive impairment were both present in 4 of 14 subjects with isolated RWA. Electromyographic activity measures increased significantly from baseline to follow-up polysomnography ("any" mentalis and both anterior tibialis muscles: 32.5 ± 9.4 versus 52.2 ± 16.6%; p = 0.004). This study provides first evidence that isolated RWA is an early biomarker of synuclein-mediated neurodegeneration. These results will have to be replicated in larger studies with longer observational periods. If confirmed, these disease findings have implications for defining at-risk cohorts for Parkinson disease.

Hypoechogenicity of brainstem raphe nuclei is associated with increased attack frequency in episodic migraine.

Reduced echogenicity of the brainstem raphe nuclei (BRN) was demonstrated in major depression, possibly indicating serotonergic dysfunction. Postulating that migraine may constitute a "chronic low serotonin syndrome," we aimed to evaluate the echogenicity of midbrain structures, including serotonergic BRN in episodic migraine. Transcranial sonography was performed in 39 patients with episodic migraine (median age 35, interquartile range (IQR): 27-47 years; 27 women) and 35 controls (median age 31, IQR: 29-47 years; 19 women). Individuals with concomitant depression were excluded. Echogenicity of BRN, substantia nigra (SN) and third ventricle width was evaluated according to an internationally established examination protocol. Hypoechogenicity of BRN was depicted in 23.1% of migraine patients and 20% of controls, showing no significant difference. Migraine patients with hypoechogenic BRN had significantly higher attack frequency (median 3, IQR 2-5 vs. 1.5, IQR 1-2 days/month; p = 0.029) and a trend toward earlier disease manifestation. The rate of hyperechogenic SN and width of the third ventricle were similar between both groups. We did not observe any differences between migraine patients with and without aura. Sonographic findings did not differ between migraine patients and controls. Hypoechogenic BRN correlated to a higher migraine attack frequency, probably indicating more severe disease activity.

Autonomic dysfunction in subjects at high risk for Parkinson's disease.

Aim of this project was to evaluate autonomic dysfunction in subjects proposed to be at high risk to develop Parkinson's disease (PD) compared to control subjects and PD patients at different disease stages. Combinations of substantia nigra hyperechogenicity (SN+) assessed by transcranial ultrasound (TCS), hyposmia, lifetime prevalence of depression and mild PD-specific motor signs were used to identify subjects at high risk for motor Parkinson's disease (HR-PD). Supine and standing blood pressure (BP), hearth rate (HR), orthostatic, urinary, sexual and bowel symptoms were evaluated in HR-PD, healthy control subjects and PD patients, divided into mild and advanced stages. The study group consisted of 113 PD patients (mild PD n=71, advanced PD, n=42), 40 HR-PD individuals and 50 controls. Compared to controls, HR-PD subjects complained more often about urinary (p=0.002) and bowel dysfunction (p=0.001) and had a higher diastolic BP drop after standing (p=0.01). The cumulative number of autonomic symptoms differentiated PD as well as HR-PD significantly from controls (p<0.001). Advanced PD patients presented often and severe orthostatic symptoms, not significantly different from mild PD after concomitant medication correction. Our results support the presence of urinary and bowel dysfunction in subjects at high risk for motor PD. Presence and severity of orthostatic symptoms was higher during stages and increase in advanced stages, at least partly due to increase in dopaminergic and conflicting medication. Understanding the progression of non-motor aspects in PD might offer the possibility to use them as targets for disease-modifying therapies.

The relationship between smoking and substantia nigra hyper-echogenicity in Parkinson's disease patients

The relationship between smoking and substantia nigra hyper-echogenicity in Parkinson's disease patients