Biomedical subjects

B Zeiler

Publications and source records attributed to B Zeiler.

4 recordsLinked to original sources

PubMed2004

Ceruloplasmin gene variations and substantia nigra hyperechogenicity in Parkinson disease.

BACKGROUND: Transcranial ultrasound may be used to detect increased iron levels of the substantia nigra (SN) in patients with Parkinson disease (PD) and in control subjects. It is not known whether iron accumulation in PD is a primary or secondary phenomenon. However, sequence variations in genes involved in iron metabolism have been linked to basal ganglia disorders. One of these is ceruloplasmin (Cp), which is vitally involved in iron transport across the cell membrane. METHODS: One hundred seventy-six patients with PD according to the UK Brain Bank criteria and 180 ethnically matched control subjects, who were previously examined for SN iron signal changes by transcranial ultrasound, were examined for mutations in the Cp gene using denaturing high-performance liquid chromatography and subsequent sequencing for verification of unequivocal signals. Immunohistochemistry of PD midbrains was performed to examine the presence of Cp in Lewy bodies. RESULTS: Five novel missense variations were detected. One of these (I63T) was found in a single PD patient. A known variation (D554E) was significantly associated with PD and the ultrasound marker for increased SN iron levels. Moreover, a third sequence variation (R793H) was found to segregate with the ultrasound marker for increased iron levels in patients and control subjects. Immunohistochemistry demonstrated that Cp co-localizes with Lewy bodies in PD. CONCLUSIONS: Detection of sequence variations in a single Parkinson disease (PD) patient or associated with the ultrasound marker for increased substantia nigra iron levels and the presence of ceruloplasmin (Cp) immunoreactivity in Lewy bodies underline a suspected role for Cp in the pathogenesis of PD. Further functional analyses are warranted to investigate whether these variations are causally linked to the complex pathogenesis of PD in a subset of cases.

Aged↗

PubMed2000

Lesion pattern in patients with multiple sclerosis and depression.

To assess if a specific lesion pattern or changes of the basal limbic system as seen in primary depression and depression associated with neurodegenerative disorders might be identified in depressive multiple sclerosis (MS) patients, we submitted 78 MS patients to a MRI examination consisting of a quantitative measurement of lesions and of hyperintense signals from the pontomesencephalic midline (raphe). Furthermore relaxometry of the pontomesencephalic midline, a transcranial ultrasound examination rating its echogenicity semiquantitatively and a standardized neurological, neuropsychiatric and neuropsychological assessment were obtained. Thirty-one patients fulfilled the DSM-IV criteria for depression. Depressed MS patients had a significantly larger temporal lesion load than non-depressed MS patients, especially on the right side. A trend of difference was detected for lesions of the right parietal lobe, the right frontal lobe, the cerebellum and the total lesion load. Neither hyperintense signals or relaxometry nor echogenicity of the region at the level of the pontomesencephalic midline were significantly different between the groups. We conclude that depression in MS patients is not associated with an alteration of the basal limbic system at the brainstem as seen in Parkinson's disease or unipolar depression but with an increased lesion load of the projection areas of the basal limbic system.

Adult↗

PubMed1999

Vulnerability of the nigrostriatal system as detected by transcranial ultrasound.

OBJECTIVE: To assess the incidence of a hyperechogenic substantia nigra (SN) by transcranial sonography (TCS) in healthy people and to evaluate whether an enlarged hyperechogenic SN area is associated with functional impairment of the nigrostriatal system. BACKGROUND AND METHODS: Until now, preclinical impairment of the nigrostriatal system could be identified only by functional neuroimaging techniques such as PET in selected groups of patients. TCS is a new, noninvasive ultrasound technique that has demonstrated an increased echogenicity of the SN in patients with PD, whereas in most healthy individuals, the SN is either barely detectable or undetectable by TCS. RESULTS: Of 330 healthy volunteers, 8.6% exhibited an increased echogenicity of the SN. From these, 10 clinically healthy individuals with distinct unilateral or bilateral hyperechogenic signals in the SN region (SN area above 0.25 cm2) underwent comprehensive motor testing, neuropsychological assessment, MRI, and [18F]-dopa PET examination. With regard to motor functions, these individuals did not differ from 10 age- and sex-matched controls with a low echogenic SN and an area of echogenic signals below 0.2 cm2. Enlargement of hyperechogenic areas in the 10 healthy individuals was associated with a marked decrease in the accumulation of [15F]-dopa in the caudate nucleus and putamen. CONCLUSIONS: Substantia nigra hyperechogenicity appears to indicate a functional impairment of the nigrostriatal system. Transcranial sonography may be a suitable method of identifying persons at risk of nigrostriatal alterations, making possible the introduction of early neuroprotective therapy.

Adolescent↗

PubMed1999

Depression in Parkinson's disease: brainstem midline alteration on transcranial sonography and magnetic resonance imaging.

Recent studies using transcranial sonography (TCS) have provided evidence of alterations in the mesencephalic midline structures in patients with unipolar depression and depression in Parkinson's disease (PD), suggesting an involvement of the basal limbic system in primary and secondary mood disorders. This study tested the hypothesis of brainstem midline abnormality in depression and investigated 31 PD patients by magnetic resonance imaging (MRI) and TCS. Signal intensity of the pontine and mesencephalic brainstem midline was rated on T2-weighted images and measured by relaxometry. In addition, two blinded investigators assessed the echogenicity of the brainstem midline by TCS. The severity of motor symptoms and depression were graded independently using standard research scales. Rating of signal intensity and T2 relaxometry of the pontomesencephalic midline structures revealed significant difference between depressed and nondepressed PD patients (P < 0.05). This corresponded to a significant reduction in mesencephalic midline echogenicity of depressed PD patients on TCS images. No correlation was found between raphe signal intensity, T2 relaxation times, or TCS echogenicity and the severity of motor symptoms or depression. This study is the first to show changes in signal intensity and T2 relaxation time of the pontomesencephalic midline structures on MRI in depressed PD patients confirming previous TCS findings. As these midline structures comprise fiber tracts and nuclei of the basal limbic system, the findings may support the hypothesis of an alteration in the basal limbic system in mood disorders.

Aged↗