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.

Neurodegenerative disease-like deep gray matter lesions can be frequently detected by transcranial sonography (TCS) in patients with multiple sclerosis (MS). Findings suggest that TCS shows changes of brain iron metabolism which correlate with future progress of MS.

The anatomical basis of cognitive dysfunction and other non-motor symptoms in multiple sclerosis (MS) is poorly understood. In MS patients, transcranial sonography (TCS) shows neurodegenerative disease-like lesions of the substantia nigra (SN) and basal ganglia, thought to reflect iron accumulation. The present study deals with the question of whether sonographic changes of SN, brainstem raphe, lenticular nucleus (LN) or caudate nucleus are related to non-motor symptoms of MS. We used TCS to investigate 54 MS patients and 54 age- and sex-matched healthy subjects. Degree of cognitive (executive) dysfunction, fatigue, depression, and urinary urge incontinence in MS patients was assessed using the Paced Auditory Serial Addition Test, the Faces Symbol Test, the Modified Fatigue Impact Scale, the Beck Depression Inventory, and the Urinary Distress Inventory. Abnormal TCS findings of SN, brainstem raphe, LN, and caudate nucleus were found in 13, 7, 11, and 6% of the healthy subjects, but in 54, 43, 62, and 41% (each, p < 0.001) of the MS patients, with similar frequency in relapsing-remitting and primary or secondary progressive MS patients. Sonographic alteration of the LN correlated with cognitive dysfunction. Combined alteration of both, LN and SN, was clearly associated with cognitive dysfunction and cognitive fatigue. The combined sonographic alteration of SN and brainstem raphe indicated severe urinary urge incontinence irrespective of the presence of spinal MS lesions. No relation was found between depression and any of the TCS findings. These findings suggest that neurodegenerative processes affecting deep brain structures contribute to cognitive and autonomic dysfunction in MS.

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

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