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M Dichgans

Publications and source records attributed to M Dichgans.

At least 19 recordsLinked to original sources
PubMed2002

[Diagnostic evaluation of the craniocervical vascular system with a 16-slice multi-detector row spiral CT. Protocols and first experiences].

PURPOSE: The newly developed 16-slice multi detector row computed tomography (MDCT) allows for isotropic imaging at rotation times under 500 ms. We aim to describe our first experiences with this novel technology in the diagnostic imaging of the craniocervical vascular system. METHODS: The craniocervical vascular system of 8 consecutive patients was examined with a standardized protocol with the new 16-slice MDCT. The volume covered included the carotid arteries from their origin at the aortic arch and the intracranial arterial and venous vessels in their entirety. Homogeneity of contrast, contrast-to-parenchyma ratios, image quality and radiation doses were assessed. RESULTS: A homogeneous vessel-to-parenchyma ratio was reached in the carotids as well as in the intracranial arterial and venous vessels. Image quality was rated as excellent in all patients. The estimated mean effective radiation dose amounted to 2.31 mSv +/-0.57, the mean dose length product to 608 mGy*cm +/-151. CONCLUSION: The newly developed 16-slice MDCT technology appears to be a promising tool in the diagnostic assessment of the cervicocranial vessels.

Aged↗
PubMed2001

NOTCH3 mutation involving three cysteine residues in a family with typical CADASIL.

Mutations in NOTCH3 are the cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary angiopathy causing stroke and vascular dementia. All CADASIL mutations identified so far result in the loss or gain of one cysteine residue within epidermal growth factor (EGF)-like repeat domains. Here an in-frame deletion causing a loss of three cysteine residues within EGF repeat 6 is reported. These data are consistent with the hypothesis that the change toward an odd number of cysteine residues within a given EGF repeat and therefore an unpaired, reactive cysteine residue is the common and critical molecular event in CADASIL.

Adult↗
PubMed2001

Reversible coma with raised intracranial pressure: an unusual clinical manifestation of CADASIL.

A 50-year-old woman presented with recurrent episodes of headache, nausea and disturbed consciousness that were fully reversible within a few days. Clinical and radiological findings suggested raised intracranial pressure, which on one occasion was confirmed by intracranial pressure monitoring. Magnetic resonance imaging performed in the asymptomatic interval disclosed a diffuse leukoencephalopathy. Brain biopsy surprisingly revealed the typical vascular changes of CADASIL and subtle endothelial alterations. The white matter showed edematous changes and reactive gliosis. Mutational analysis of the Notch3 gene revealed a previously unreported mutation. We suggest that a transient disturbance of the blood-brain barrier related to the underlying vascular pathology may have caused this unusual presentation of CADASIL.

Coma↗
PubMed2001

A magnetic resonance imaging study of the cervical cord of patients with CADASIL.

The authors obtained MR and magnetization transfer (MT) imaging of the cervical cord from 25 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). They found no conventional MR abnormalities, but a reduced peak height of the MT ratio (MTR) histogram. This suggests a reduced amount of "truly" normal cord tissue in CADASIL. A significant correlation was found between the extent of brain lesions and cord MTR, suggesting wallerian degeneration as the substrate of the cord MTR changes.

Adult↗
PubMed2001

Altered white and gray matter metabolism in CADASIL: a proton MR spectroscopy and 1H-MRSI study.

OBJECTIVE: Subcortical white matter hyperintensities (WMH) and small cystic lesions are the radiologic hallmark of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary angiopathy causing stroke in young adults. To further characterize the cerebral pathology in vivo we analyzed metabolite concentrations in normal and abnormal appearing brain tissue using single and multiple voxel proton MR spectroscopy (1H-MRS and 1H-MRSI). METHODS: Twenty patients with CADASIL and 21 age-matched controls were studied with 1H-MRSI at the level of the centrum semiovale; short echo time 1H-MRS was performed in six patients (WMH) and 10 controls. LCModel fits were used to estimate absolute and relative concentrations of N:-acetylaspartate (NAA), choline-containing compounds (Cho), total creatine (Cr) within WMH, normal appearing white matter (NAWM), and cortical gray matter (GM) as well as myo-inositol (mI) and lactate in WMH. RESULTS: 1H-MRSI-Patients with CADASIL showed significantly reduced NAA, Cho, Cr, and total metabolite content (Met(tot)) in WMH and NAWM. Normalization to Met(tot) revealed that NAA/Met(tot) was reduced in all regions, whereas Cho and Cr were relatively elevated in WMH. Short echo time 1H-MRS showed decreased NAA, Cr, Met(tot), and NAA/Met(tot) and elevated mI/Met(tot) and lactate in WMH. Metabolite changes were larger in severely affected subjects. Rankin scores correlated negatively with NAA/Met(tot) (all regions) and NAA/Cho (WMH), and positively with Cho/Met(tot) (WMH) and Cr/Met(tot) (NAWM). CONCLUSION: Marked metabolic abnormalities were observed in abnormal and normal appearing white matter in patients with CADASIL. The findings suggest axonal injury, enlarged extracellular spaces, myelin loss, and gliosis. The cortical abnormalities may reflect structural damage or functional neuronal impairment secondary to white matter pathology. NAA reductions were correlated with clinical disability emphasizing the clinicopathologic relevance of axonal injury in CADASIL.

Adult↗
PubMed2001

Inherited Myoclonus-dystonia syndrome: narrowing the 7q21-q31 locus in German families.

Genetic studies were performed in four German families with autosomal dominant myodonus-dystonia syndrome. Mutations in the D2 dopamine receptor gene, which have been implicated in this disorder, were excluded in all four families by linkage analysis and direct sequencing. All four families supported linkage to the second reported locus on chromosome 7q21 with a combined maximum multipoint lod score of 5.99. The observation of key recombinations in one family refined the disease locus to a 7.2 cM region flanked by the markers D7S652 and D7S2480.

Adolescent↗
PubMed2001

Differential lesion patterns in CADASIL and sporadic subcortical arteriosclerotic encephalopathy: MR imaging study with statistical parametric group comparison.

PURPOSE: To differentiate lesion patterns in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) from those in patients with sporadic subcortical arteriosclerotic encephalopathy (sSAE). MATERIALS AND METHODS: Magnetic resonance (MR; T2-weighted and fluid-attenuated inversion-recovery) images obtained in 28 patients with CADASIL were compared with images obtained in 24 patients with sSAE by using an automated pixel-based group comparison with statistical parametric mapping and regional semiquantitative rating. RESULTS: Visual rating showed higher lesion scores for CADASIL in the temporal and temporopolar white matter (WM). Statistical parametric mapping group analysis independently revealed more extensive bilateral involvement of the anterior temporal and superior frontal WM in CADASIL. There were bilateral signal intensity reductions within the dentate nucleus, deep cerebellar WM, crus cerebri, and thalamus. Lesions extended remarkably more often into arcuate fibers in the temporopolar and paramedian superior frontal lobes in CADASIL. Linear discriminant analysis was used to classify 96% (50 of 52) of the cases correctly, with temporopolar WM and arcuate fiber involvement contributing most to the discrimination function. CONCLUSION: The presented MR imaging criteria are useful in the diagnostic work-up in patients with leukoencephalopathy and help to differentiate CADASIL from sSAE. The observed pattern of vulnerability in CADASIL suggests future directions for research in the pathophysiology of this disorder. In addition, the study demonstrates the potential of automated image analysis to explore MR imaging lesion patterns.

Aged↗
PubMed2001

Reduced cerebrovascular CO(2) reactivity in CADASIL: A transcranial Doppler sonography study.

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukencephalopathy (CADASIL) is a hereditary angiopathy caused by mutations in Notch3. Cerebral microvessels show an accumulation of granular osmiophilic material in the vicinity of degenerating vascular smooth muscle cells. To study cerebrovascular function in CADASIL, we performed measurements on cerebral hemodynamics by using transcranial Doppler sonography. METHODS: Middle cerebral artery (MCA) mean blood flow velocity (MFV), cerebrovascular CO(2) reactivity, and the resistance index were measured by bilateral transcranial Doppler sonography in 29 CADASIL individuals (mean age, 49.0+/-2.4 years) and an equal number of age- and sex-matched control subjects. RESULTS: Compared with control subjects, CO(2) reactivity was reduced in CADASIL (33.4+/-2.7% versus 45.3+/-3.0%; P:<0.01). This difference remained significant when only nondisabled CADASIL individuals (Rankin=0, n=21) were included in the analysis (P:<0.05). CO(2) reactivity was significantly lower in disabled than in nondisabled CADASIL individuals (24.5+/-2.7% versus 36.8+/-3.4%; P:<0.05). MCA MFV was reduced in CADASIL (45.6+/-2.2 cm/s versus 54.2+/-2.4 cm/s; P:<0.05) and correlated negatively with age both in affected individuals (r=-0.314; P:<0.05) and control subjects (r=-0.339; P:<0.05). Resistance index was not significantly altered (59.0+/-1.0% versus 57.7+/-1.2%; P:=0.42). CONCLUSIONS: In CADASIL, there is a reduction of both CO(2) reactivity and basal MCA MFV. The reduced CO(2) reactivity suggests functional impairment of cerebral vasoreactivity probably related to vascular smooth muscle cell dysfunction. The reduction of CO(2) reactivity in nondisabled CADASIL individuals suggests an early role of impaired cerebral vasoreactivity in the evolution of the disease.

Adult↗
PubMed2001

Correlations between clinical findings and magnetization transfer imaging metrics of tissue damage in individuals with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

BACKGROUND AND PURPOSE: We obtained magnetization transfer imaging (MTI) scans from individuals with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) (1) to investigate the presence, extent, and nature of pathology in white and gray matter outside proton density (PD)-visible lesions; (2) to quantify the degree of tissue damage occurring in lesions seen on PD-weighted scans; and (3) to correlate MTI-derived measures of disease burden with age, physical disability, and cognitive performance. METHODS: Dual-echo, T1-weighted, and MTI scans of the brain were obtained from 33 individuals with CADASIL and 12 control subjects. Magnetization transfer ratio (MTR) values from PD-visible lesions, normal-appearing white matter (NAWM), and normal-appearing gray matter (NAGM) were measured. Histograms of MTR from the whole brain and normal-appearing brain tissue were also produced. RESULTS: All MTR values from NAWM and NAGM regions studied were significantly lower for individuals with CADASIL than for control subjects, with the exception of those obtained from the NAWM of the infratentorial structures and the NAGM of the occipital cortex. The average MTR from PD lesions in individuals with CADASIL was significantly lower than that from all the NAWM regions. Average MTR and peak location from whole-brain and normal-appearing brain tissue histograms were significantly lower for individuals with CADASIL than for control subjects. MTR values from NAWM were strongly correlated with the extent of macroscopic lesions and their average MTR. Apart from NAGM, average MTR from all other tissues studied significantly decreased with increasing age, physical disability, and cognitive impairment. CONCLUSIONS: PD lesions of individuals with CADASIL have variable degrees of tissue damage. Brain tissue outside PD abnormalities is also damaged. This study suggests that the extent and the severity of the brain tissue damage are critical factors in determining clinical status in CADASIL.

Age Factors↗
PubMed2001

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: decrease in regional cerebral blood volume in hyperintense subcortical lesions inversely correlates with disability and cognitive performance.

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an arteriopathic syndrome related to a genetic defect on chromosome 19. Characteristic changes in CADASIL can be observed onT2-weighted MR images in the subcortical white matter. The purpose of this study was to measure changes of regional cerebral blood volume (rCBV) with dynamic contrast-enhanced MR imaging and to correlate the changes to disability and cognitive performance. METHODS: We obtained rCBV measurements of 24 individuals with proven CADASIL on a 1.5-T MR imaging unit. A susceptibility-weighted MR imaging sequence was used for bolus tracking. Principles of the indicator dilution theory were applied to estimate values of absolute rCBV (mL/100 g). Disability was determined by using the Rankin scale, and overall cognitive performance was assessed by using the Mini-Mental State Examination. RESULTS: The mean rCBV in the subcortical white matter that was hyperintense on the T2-weighted images (2.7 +/- 0.8 mL/100 g) was significantly lower than the rCBV in the white matter that appeared normal on the T2-weighted images (4.4 +/- 1.3 mL/100 g) (P <.05). The mean rCBV in the gray matter was within the normal range (8.3 +/- 1.7 mL/100 g). Both cognitive impairment and disability negatively correlated with rCBV in the subcortical white matter that was hyperintense (P <.05) but not with rCBV in the normal appearing white matter. rCBV did not correlate with age. CONCLUSION: rCBV measured in the hyperintense subcortical white matter in individuals with CADASIL was decreased and inversely correlated with disability and cognitive impairment.

Adult↗
PubMed2000

Clinical characteristics and frequency of the hereditary restless legs syndrome in a population of 300 patients.

There is a genetic contribution to the idiopathic restless legs syndrome (iRLS). An autosomal dominant mode of inheritance is suspected, but as yet no gene has been identified. To assess the frequency and characteristics of the hereditary restless legs syndrome (RLS) in comparison to those of non-hereditary RLS, we analysed the clinical data of 300 RLS patients. All 300 patients diagnosed as RLS according to the criteria of the International RLS Study Group were examined using a standard questionnaire covering demographic data, family history, clinical symptoms, subjective sleep disturbances and course of the disease. In all patients a complete neurological examination was performed, and in selected cases electrophysiological examinations and polysomnographic studies. Family history was rated as definitely positive when at least one first-degree relative was examined and classified as RLS according to the criteria by one of the authors. If it proved impossible to contact family members to verify reports of a family history, the patients were classified as only having a "possible positive family history." 232 of the 300 patients had iRLS and 68 secondary RLS due to uremia (uRLS). 42.3% of the patients with iRLS and 11.7% of those with uRLS were classified as having "definite positive" hereditary RLS, with a further 12.6% of iRLS patients and 5.8% of uRLS patients as having "possible positive" hereditary RLS. Patients with definite hereditary RLS were significantly younger at the age of onset than those with a negative family history (35.45 vs. 47.17 years, p < 0.05). The clinical characteristics of the disease were similar in both groups, except that women with hereditary RLS experienced a worsening of symptoms during pregnancy (19.1% vs. 2.6%, p < 0.05). Our study shows that patients with hereditary RLS may experience an earlier onset of the disease. Hereditary and non-hereditary RLS present with similiar clinical signs and symptoms.

Adaptation, Psychological↗
PubMed2000

Aura in some patients with familial hemiplegic migraine can be stopped by intranasal ketamine.

Migraine aura is probably caused by cortical-spreading depression. No treatment for acute and severe migraine aura has been described previously. The effect of ketamine (25 mg intranasally) was studied in 11 patients with severe, disabling auras resulting from familial hemiplegic migraine. In five patients ketamine reproducibly reduced the severity and duration of the neurologic deficits, whereas in the remaining six patients no beneficial effect was seen. Ketamine offers, for the first time, a possible treatment option for severe and prolonged aura.

Administration, Intranasal↗
PubMed2000

Small in-frame deletions and missense mutations in CADASIL: 3D models predict misfolding of Notch3 EGF-like repeat domains.

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a hereditary microangiopathic condition causing stroke in young adults. The responsible gene has recently been identified as the Notch3 gene. Notch3 encodes a large transmembrane receptor with 34 extracellularly localised epidermal growth factor-like (EGF) repeat domains. We screened 71 unrelated CADASIL families for mutations in two exons coding for the first five EGF-like repeats and found mutations in 70% of the families (n = 50). Two types of mutations were identified: 48 families (96%) had missense mutations and two families (4%) had small in-frame deletions. Seven mutations occurred multiple times. All of them are C to T transitions that affect CpG dinucleotides, suggesting that their multiple occurrence is due to the hypermutability of this sequence. All mutations, including the two deletions, result in the gain or loss of a cysteine residue, thus substantiating the pivotal role of an uneven number of cysteine residues within EGF-like repeat domains of Notch3 in the pathogenesis of CADASIL. To study the potential effects of these mutations 3D homology models of the first six EGF domains were generated on the basis of NMR data from human fibrillin-1. These models predict domain misfolding for a subset of mutations.

Amino Acid Sequence↗
PubMed2000

Motor cortex excitability in patients with migraine with aura and hemiplegic migraine.

We studied the excitability of the motor cortex using transcranial magnetic stimulation (TMS) in 12 patients with migraine with aura (MA) and nine patients with familial hemiplegic migraine (FHM). Motor thresholds at rest, the duration of the cortical and peripheral silent period and intracortical inhibition and facilitation using paired-pulse TMS at intervals of 2 to 15 ms were measured with patients free of attacks for at least 48 h. In contrast to previous reports we could not find any significant differences between patient groups and compared to controls (n=17) in the parameters tested. The results suggest that there are no interictal changes of excitability of the motor cortex in migraine. This study does not support the concept of general cortical hyperexcitability in migraine secondary to a genetic predisposition or a structural alteration of inhibitory interneurones in the cortex due to repeated parenchymal insults during attacks.

Adult↗