Echogenicity Of Brainstem Raphe Research Articles

Hypoechogenicity of brainstem raphe in long-COVID syndrome–less common but independently associated with depressive symptoms: a cross-sectional study

ObjectiveLong coronavirus disease (Long-COVID) syndrome is a hitherto poorly understood phenomenon with a broad spectrum of symptoms, including depression and anxiety. Depressive symptoms have been associated with brainstem raphe (BR) alterations in transcranial sonography (TCS) that might reflect dysfunction of the serotonergic system. The primary aim was to investigate the connection of BR alterations with depressive and anxiety symptoms in patients with Long-COVID syndrome.MethodsIn a cross-sectional study design, we included outpatients fulfilling the criteria of Long-COVID syndrome. All patients were examined by TCS in the axial plane with focus on BR signal alterations. The Hospital Anxiety and Depression Scale (HADS) was used to test for symptoms of anxiety and depression.ResultsWe included n = 70 patients with Long-COVID syndrome, of which 28.6% (n = 20) exhibited a reduced echogenicity of BR in the TCS examination. Patients with hypoechogenic BR had higher subscores for anxiety and depression compared to normoechogenic patients (HADS depression: median 8 versus 5.5, p = 0.006; HADS anxiety: median 9 versus 6.5, p = 0.006). After adjustment for reasonable confounders, only the odds ratio (OR) for relevant depressive symptoms was higher among Long-COVID patients with hypoechogenic raphe (adjusted OR 3.884, 95% CI 1.244–12.123).DiscussionHypoechogenic BR alterations are independently associated with depressive symptoms in Long-COVID patients but are not highly frequent. Future studies should investigate whether the hypoechogenicity of the BR is a direct consequence or whether it reflects a priori a higher susceptibility to depressive symptoms after COVID-19, thus enabling to identify COVID-19 patients at higher risk of developing Long-COVID depressive symptoms.

Transcranial sonography imaging of brainstem raphe, substantia nigra and cerebral ventricles in patients with geriatric depression.

Geriatric depression is a special condition associated with a chronic course, treatment resistance and vascular processes. However, its neurobiology has not been fully elucidated. There is no study in geriatric depression evaluating deep brain structures with transcranial sonography (TCS) which is a low-cost, non-invasive and practical tool. The present study aimed to evaluate the changes in the echogenicity of brainstem raphe (BR), substantia nigra (SN) and ventricular diameters by TCS in association with cognitive dysfunctions in patients with geriatric depression. Echogenicity of BR and SN were assessed and transverse diameters of the third ventricle and frontal horns of the lateral ventricles were measured by TCS in 34 patients with DSM-5 major depression and 31 healthy volunteers aged 60 and older. Cognitive functions were evaluated by using Mini Mental State Examination, Montreal Cognitive Assessment Tool, Clock Drawing Test and Subjective Memory Complaints Questionnaire. Although depressed patients had more subjective memory complaints than controls, they had similar cognitive performances. Reduced echogenicity (interrupted/invisible echogenic line) of BR was found to be significantly higher and the ventricular diameters were larger in the depressed group. There was no difference between the groups in terms of SN echogenicity. There was no correlation between ventricular diameters and depression severity or cognitive functions. Results of the present study are important in terms of pointing out neurobiological changes related to geriatric depression which are in parallel with the results of the studies in younger patients with depression. However, long-term follow-up studies are required for accurate differentiation of neurocognitive disorders.

Transcranial Sonography Findings in Depression in Association With Psychiatric and Neurologic Diseases: A Review.

The transcranial sonography (TCS) finding of reduced echogenicity of brainstem raphe (hypoechogenic BR) has been associated with depressive states. Here, we review the TCS studies in subjects with depressive disorders and with depression related to degenerative brain diseases, and compare the frequency and clinical correlates of hypoechogenic BR in these reports. Summarizing the data published so far, hypoechogenic BR is present in 67% (range, 37-95%) of depressed but only in 15% (5-36%) of nondepressed subjects without history of neurodegenerative disease. The finding of hypoechogenic BR in these subjects is associated with a relative risk of 3.03 (95% CI, 2.44-3.75; P < .001) of being diagnosed with depression. In patients with Parkinson's disease, hypoechogenic BR is present in 63% (35-92%) of depressed but only in 27% (10-62%) of nondepressed patients, resulting in a relative risk of 2.18 (95% CI, 1.80-2.66; P < .001) of being diagnosed with depression. Hypoechogenic BR is associated with depression in a number of neurological disorders such Huntington's disease, idiopathic Rapid Eye Movement (REM) sleep behavior disorder, myotonic dystrophies, and cerebral small vessel disease. Although some studies did not show any relationship between BR echogenicity and severity of depression, others suggest an association with higher severity of depression, or even with suicidal ideation. In one study BR hypoechogenicity was found to be associated with better responsivity to serotonin reuptake inhibitors. Further studies are warranted to compare the TCS findings of BR alteration with post-mortem histopathological findings, and with genetic variants related to cerebral serotonin metabolism.

Transcranial sonography of brainstem structures in panic disorder

Panic disorder has been associated with altered serotonin metabolism in the brainstem raphe. The aim of study was to evaluate the BR echogenicity on transcranial sonography (TCS) in panic disorder. A total of 96 healthy volunteers were enrolled in the “derivation” cohort, and 26 healthy volunteers and 26 panic disorder patients were enrolled in the “validation” cohort. TCS echogenicity of brainstem raphe and substantia nigra was assessed on anonymized images visually and by means of digitized image analysis. Significantly reduced brainstem raphe echogenicity was detected more frequently in panic disorder patients than in controls using both visual (68% vs. 31%) and digitized image analysis (52% vs. 12%). The optimal cut-off value of digitized brainstem raphe echogenicity indicated the diagnosis of panic disorder with a sensitivity of 64% and a specificity of 73%, and corresponded to the 30th percentile in the derivation cohort. Reduced brainstem raphe echogenicity was associated with shorter treatment duration, and, by trend, lower severity of anxiety. No relationship was found between echogenicity of brainstem raphe or substantia nigra and age, gender, severity of panic disorder, or severity of depression. Patients with panic disorder exhibit changes of brainstem raphe on TCS suggesting an alteration of the central serotonergic system.

Clinical, genetic, and brain sonographic features related to Parkinson’s disease in Gaucher disease

Homozygous or compound heterozygous mutations in the glucocerebrosidase gene cause Gaucher disease. Moreover, heterozygous glucocerebrosidase gene mutations represent the most common genetic risk factor for Parkinson's disease (PD) known so far. Substantia nigra (SN) hyperechogenicity, a sonographic feature thought to reflect iron accumulation, has been described in both PD and Gaucher disease patients. Here we studied how clinical, genetic, and brain sonographic findings relate to the occurrence of PD in Gaucher disease. Sixteen Gaucher disease patients, 12 PD patients, and 32 control subjects were enrolled. The glucocerebrosidase genotypes were identified by DNA sequencing. All subjects underwent transcranial ultrasound, and eight Gaucher disease patients additionally MRI for comparison with SN ultrasound findings. SN hyperechogenicity and reduced echogenicity of brainstem raphe were more frequent in Gaucher disease patients (62, 37 %) than in controls (12, 12 %; p < 0.001, p < 0.05). SN hyperechogenicity in Gaucher disease patients was unrelated to type or severity of glucocerebrosidase gene mutation, but correlated with iron-sensitive MRI-T2 hypointensity of SN pars compacta, and with age at start of enzyme replacement therapy. While none of the five Gaucher disease patients with signs of PD (definite PD, n = 4; early PD, n = 1) had severe glucocerebrosidase gene mutations known to cause neuronopathic Gaucher disease, all carried a N370S allele, previously reported to predict non-neuronopathic Gaucher disease. Hyposmia, higher non-motor symptoms score (constipation, depression, executive dysfunction), and SN hyperechogenicity were characteristic features of Gaucher disease-related PD. We conclude that the combined clinical, genetic, and transcranial sonographic assessment may improve the PD risk evaluation in Gaucher disease.

Substantia nigra hyperechogenicity in depressive subjects relates to motor asymmetry and impaired word fluency

Substantia nigra hyperechogenicity (SNH) is a characteristic transcranial sonography (TCS) finding in Parkinson's disease (PD). SNH, found also in about 10% of healthy adults, was related to a subclinical malfunction of the nigrostriatal dopaminergic system on positron emission tomography studies. Both, liability for developing PD and frequency of SNH were found to be increased in depressed subjects. Here, we investigated whether SNH in depression is related to motor or cognitive abnormalities resembling early PD. Fourty-one patients with major depressive disorder and 15 with adjustment disorder with depressed mood were studied clinically and with TCS. Frequency of SNH was similar in both groups (39, 33%; Chi-square test, P = 0.70). Larger SN echogenic size correlated with larger right-to-left asymmetry of finger tapping (Spearman test, r = 0.37, P = 0.009) and lower verbal fluency (r = -0.35, P = 0.038). These correlations were stronger in patients at ages >/= 50 years (r = 0.52, P = 0.007; r = -0.50, P = 0.020), and, independently from age, in patients with reduced echogenicity of brainstem raphe suggested to reflect alteration of the serotonergic system (r = 0.40, P = 0.045; r = -0.51, P = 0.044). Whereas bilateral sum score of finger tapping was negatively correlated with severity of depression on the beck depression inventory (r = -0.50, P = 0.001) and the Hamilton depression rating scale (r = -0.34, P = 0.019), no correlation was found between depression severity and tapping asymmetry, or between depression severity and verbal fluency. Data suggest that TCS detects a subgroup of patients with depression characterized by symptoms of early parkinsonism who are possibly at an elevated risk of later developing definite PD.

Parkinson's disease-like midbrain sonography abnormalities are frequent in depressive disorders

Substantia nigra (SN) hyperechogenicity is a characteristic transcranial sonography (TCS) finding in idiopathic Parkinson's disease. SN hyperechogenicity, found also in approximately 10% of healthy adults, was related to a subclinical malfunction of the nigrostriatal dopaminergic system on PET studies and is, therefore, thought to represent a risk marker for Parkinson's disease. Epidemiological findings suggest an increased risk in subjects with depression. To find out whether frequency of SN hyperechogenicity is increased in depression, we performed TCS of brainstem and basal ganglia in 200 subjects: 55 controls without depression and without Parkinson's disease, 55 subjects with depression without Parkinson's disease (D+ PD-), 45 Parkinson's disease patients without depression (D- PD+) and 45 Parkinson's disease patients with depression (D+ PD+). Marked SN hyperechogenicity was found in 13% of controls, 40% of D+ PD- (chi2 test, P = 0.001), 69% of D- PD+ (vs D+ PD-, P = 0.004) and 87% of D+ PD+ patients (vs D- PD+, P = 0.04). Reduced echogenicity of brainstem raphe, thought to reflect alteration of the serotonergic system, was more frequent in depressed than in non-depressed subjects, irrespective of presence of Parkinson's disease, confirming earlier reports. The combined finding of marked SN hyperechogenicity and reduced raphe echogenicity in Parkinson's disease patients, however, was clearly associated with a history of depression prior to Parkinson's disease onset, whereas in D+ PD- patients this combined TCS abnormality was related to motor asymmetry. In D+ PD+ patients with depression prior to Parkinson's disease onset (n = 12), larger SN echogenic sizes correlated with younger age at Parkinson's disease onset (Spearman test, r = -0.607, P = 0.036). TCS findings of other basal ganglia did not differ between the groups studied. Data suggest that in subjects with depression nigrostriatal vulnerability is frequent, and that TCS might be useful to detect individuals at risk for developing Parkinson's disease.

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.

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

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