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H Grehl

Publications and source records attributed to H Grehl.

At least 19 recordsLinked to original sources
PubMed2003

[Age dependence of Doppler parameters in the basal cerebral arteries evaluated by transcranial color-coded duplex sonography. Reference data from 290 volunteers].

AIM: In this study the Doppler parameters of the basal intracranial arteries and the insonation in axial and coronary plane by temporal approach were established in healthy volunteers of all age groups with transcranial color-coded duplex sonography (TCDS). METHODS: 290 healthy probands (age 0 to 91 years) were investigated through the temporal and transnuchal ultrasound window. The angle corrected flow velocities and the resistance indices of the basal brain arteries were measured. RESULTS: The flow velocities rapidly increase in children (from 3 years up to puberty) and gradually decrease with increased age. Vice versa, the resistance indices decrease in children and increase in older people. The flow velocities show significant differences by axial and coronary insonation in certain arteries of the circle of Willis. CONCLUSION: The Doppler parameters of the basal intracranial arteries evaluated with TCDS depend from age. The flow velocities and resistance indices are similar in children and older people. The coronary transtemporal approach is considered a useful completion of the axial investigation.

Adolescent↗
PubMed2001

[Correlation of clinical and magnetic resonance imaging findings in patients with brainstem infarction].

The aim of this study was the comparison of clinical and neurological findings in 30 patients presenting with ischemic brainstem lesions. These were localized in the midbrain in 4 cases, in the medulla in 12 cases and in the pons in 11 cases, while the remaining three patients demonstrated combined lesions. Symptoms were lesions of the pyramidal tract in 77% of cases, vertigo in 57% of cases, speech disturbances in 40% of cases and gait ataxia in 37% of cases. Cranial nerve lesions were evident in 87% of patients, while 33% of patients demonstrated a Horner syndrome. Brainstem lesions were diagnosed in 22 (73%) of patients on magnetic resonance imaging, while all 30 patients had clinical signs suggestive of brainstem lesions. We conclude that neuroradiological studies can provide helpful information regarding patients with brainstem lesions, but by no means replace exact neurological examination.

Adult↗
PubMed2000

PMP22 Thr118Met is not a clinically relevant CMT1 marker.

It is controversial if peripheral myelin protein 22 gene (PMP22) Thr118Met represents a functionally irrelevant polymorphism or, since hemizygosity for this variant has been found in two patients with Charcot-Marie-Tooth disease type 1 (CMT1 patients), it can act as a recessive CMT1 mutation. To shed further light on this variant and its diagnostic value we searched for carriers in 1018 individuals from the German general population, in 104 probands with hereditary neuropathy with liability to pressure palsies (HNPP) who were carriers of the 1.5-Mb deletion frequently associated with this disorder, in 187 patients with the 1.5-Mb duplication, and in 22 patients with a CMT1 phenotype who did not have any detectable anomaly in the PMP22 gene. Using allele-specific PCR we identified 14 [allele frequency (AF)=0.007] in the German general population, one (AF=0.01) in the HNPP group and six (AF=0.016) and two (AF=0.05) carriers of the PMP22 Thr118Met mutation in the CMT1 groups with and without gene defect. Carriers from all groups showed nerve conduction velocities which did not differ from typical values for these groups. We conclude that the hemizygous occurrence of the 118Met allele does not usually cause CMT1. Because of previous reports on its association with disease, and because its allele product shows abnormalities in in vitro expression systems, it seems possible that this mutation, together with yet unidentified factors, predisposes to CMT1. Alternatively, previously reported disease associations occurred by chance, and the 118Met allele causes biochemical abnormalities irrelevant for CMT1 formation. In either case this mutation is not a clinically relevant disease marker.

Biomarkers↗
PubMed1999

[Secondary normal pressure hydrocephalus. A complication of chronic neuroborreliosis].

We report about a 57-year-old patient suffering from the typical symptoms of normal-pressure hydrocephalus (NPH) including gait disturbance, urinary incontinence, and mental deterioration. CSF analysis established the diagnosis of chronic active Lyme neuroborreliosis with lymphocytic pleocytosis and intrathecal Borrelia burgdorferi antibody production. After several weeks of i.v. antibiotic treatment we observed normalization of CSF parameters as well as a clear improvement of clinical symptoms so that surgical shunting was no longer indicated. Interference with subarachnoid CSF flow may be a possible cause of the observed symptomatic NPH in a patient with chronic Lyme neuroborreliosis.

Borrelia burgdorferi Group↗
PubMed1998

Charcot-Marie-Tooth disease type 1A and hereditary neuropathy with liability to pressure palsies: a SacI polymorphism in the proximal CMT1A-REP elements may lead to genetic misdiagnosis.

A male patient with clinical signs and symptoms of a demyelinating neuropathy was shown to have a duplication of the 1.5-Mb region on chromosome 17p11.2 by means of two-color fluorescence in situ hybridization (FISH). This duplication is typical for the vast majority of Charcot-Marie-Tooth type 1A (CMT1A) cases. Analysis of DNA extracted from peripheral blood used to detect an EcoRI/SacI 3. 2-kb junction fragment with probe pLR7.8 confirmed the CMT1A duplication, but also revealed a 7.8-kb fragment usually observed in patients with a hereditary neuropathy with liability to pressure palsies (HNPP). Both fragments observed in one patient canot result from one unequal crossover. In EcoRI/SacI Southern hybridization experiments with probe pLR7.8 DNA of his healthy parents also revealed a 7.8-kB restriction fragment. A subsequent two-color FISH analysis, however, indicated a normal status for interphase nuclei of the parents. Hence we hypothesize that the 7.8-kb fragment observed in our patient and his parents is not the product of unequal crossover during meiosis but due to a polymorphism of the SacI site in a proximal CMT1A-REP element.

Adult↗
PubMed1998

Expression pattern of the peripheral myelin protein 22kDa (PMP22) in neural and non-neural tissue types of adult wildtype and Trembler mice--a comparative study.

The Trembler mouse was the first animal model for Charcot-Marie-Tooth disease type 1 (CMT1), one of the most frequent inherited peripheral neuropathies in man. In Trembler mouse a Gly150Asp amino acid exchange in the peripheral myelin protein 22kDa (PMP22) gene was identified as causative reason for this hypertrophic neuropathy. For most of the CMT patients suffering from the subtype 1A a duplication of the PMP22 gene is found (gene dosage effect); but several PMP22 point mutations, such as that determining the TremblerJ mouse, have also been described. Since PMP22 is expressed in neural, as well as in non-neural tissues, the expression pattern of PMP22 in different tissues seems to be of highest interest for a better understanding of the hypothesized dual function of this protein. We studied different wildtype (wt) and Trembler (Tr) mouse tissues for PMP22 expression by means of radioactive in situ hybridization (RISH) and immunohistochemistry. A PMP22 expression was found in some of the non-neural and in all neural tissue types studied. Our in situ study clearly demonstrated, that PMP22 mRNA expression in non-neural tissues is not due to peripheral innervation. In non-neural tissues no difference in the expression pattern or intensity between wt and Tr mice was detectable, whereas PMP22 expression in the peripheral nervous system (PNS) of the Tr mouse was extremely reduced. Immunohistochemical analysis of sciatic nerve sections revealed the same maldistribution of PMP22 in Tr mice as in sural nerve biopsies of CMT1 patients.

Animals↗
PubMed1997

Molecular diagnosis of PMP22-associated neuropathies using fluorescence in situ hybridization (FISH) on archival peripheral nerve tissue preparations.

Charcot-Marie-Tooth (CMT) syndrome type 1 and tomaculous neuropathy, also called hereditary neuropathy with liability to pressure palsies (HNPP), represent two groups of neurological disorders with different subtypes, which can be distinguished at the molecular level. It is known that a 1.5-mb region on chromosome 17p11.2-12, which includes the gene for the peripheral myelin protein 22 kDa (PMP22), is duplicated in more than 95% of patients with CMT type 1A (CMT1A; gene dosage 3) and is deleted in about 90% of subjects suffering from HNPP (gene dosage 1). This duplication/deletion can be detected reliably by interphase-two-color fluorescence in situ hybridization (FISH). We report here a technique for extraction of nuclei from paraffin-embedded and cryofixed sural nerve biopsies for precise molecular diagnosis, employing interphase-two-color FISH in clinically diagnosed CMT1 or HNPP patients. Following this technique we were able to identify six CMT1A duplications in 13 clinically diagnosed CMT1 cases and five HNPP deletions in 6 clinically diagnosed HNPP cases; 8 control persons were included in this study. This is the first report on the use of FISH in the detection of 17p11.2-12 duplication and deletion in archival biopsy material.

Adolescent↗
PubMed1997

Clinical and morphological phenotype of HMSN 1A mosaicism.

Clinical, neurophysiological and morphological studies on a patient with mosaicism of the 17p11.2 duplication were performed in detail for the first time. Since duplication occurs during paternal meiosis, a somatic reversion is suggested, leading to mosaicism. The proportion of nuclei with duplication varied markedly between 49% in blood cells and 74% in tissue from the sural nerve. Clinically, mild symptoms of a motor and sensory neuropathy were present. However, neurophysiological changes and findings in the sural nerve biopsy were consistent with a typical hereditary motor and sensory neuropathy type 1 (HMSN 1). Differing clinical findings in patients with mosaicism of the 17p11.2 duplication may be explained by a varying degree and/or time of reversion.

Adult↗
PubMed1997

Detection of the CMT1A/HNPP recombination hotspot in unrelated patients of European descent.

Charcot-Marie-Tooth type 1 disease (CMT1) and hereditary neuropathy with liability to pressure palsies (HNPP) are common inherited disorders of the peripheral nervous system. The majority of CMT1 patients have a 1.5Mb tandem duplication (CMT1A) in chromosome 17p11.2 while most HNPP patients have a deletion of the same 1.5 Mb region. The CMT1A duplication and HNPP deletion are the reciprocal products of an unequal crossing over event between misaligned flanking CMT1A-REP elements. We analysed 162 unrelated CMT1A duplication patients and HNPP deletion patients from 11 different countries for the presence of a recombination hotspot in the CMT1A-REP sequences. A hotspot for unequal crossing over between the misaligned flanking CMT1A-REP elements was observed through the detection of novel junction fragments in 76.9% of 130 unrelated CMT1A patients and in 71.9% of 32 unrelated HNPP patients. This recombination hotspot was also detected in eight out of 10 de novo CMT1A duplication and in two de novo HNPP deletion patients. These data indicate that the hotspot of unequal crossing over occurs in several populations independently of ethnic background and is directly involved in the pathogenesis of CMT1A and HNPP. We conclude that the detection of junction fragments from the CMT1A-REP element on Southern blot analysis is a simple and reliable DNA diagnostic tool for the identification of the CMT1A duplication and HNPP deletion in most patients.

Blotting, Southern↗
PubMed1996

Multifocal motor neuropathy: clinical and electrophysiological findings.

Multifocal motor neuropathy (MMN) can be differentiated from motor neuron disease by electrophysiological evidence of conduction block. To increase the probability of recording conduction block, we studied the whole nerve length including proximal segments in 84 patients with pure motor syndromes, using a special stimulation technique. In 8 patients, the diagnosis of MMN was confirmed by electrophysiological evidence of conduction block or temporal dispersion. The typical clinical picture of MMN with chronic progressive, asymmetrical, marked distal weakness was observed in our patients. Electrophysiological routine tests of distal nerves were usually normal except in nerve segments with conduction block. In 4 patients, conduction block could be recorded only in proximal nerve segments or spinal roots. All patients showed rapid improvement of clinical features and parallel reduction of conduction block during or after high-dose intravenous immunoglobulin (ivIG) therapy, supporting the diagnosis of an immune-mediated neuropathy. Three of them are now in remission without any therapy, whereas 5 still receive a regular ivIG course every 2-12 weeks as long-term treatment. In all patients with pure or predominantly motor syndromes and normal findings in electrophysiological routine tests of distal nerve segments, there should be proximal conduction block studies to avoid overlooking a treatable disorder such as MMN.

Adolescent↗
PubMed1996

[Immunoglobulin therapy of chronic inflammatory neuropathies].

High-dose intravenous immunoglobulins (ivIg) are an effective therapy in chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). In both diseases, data regarding ivIg long-term treatment are sparse. Therapy with ivIg was performed in 18 patients with CIDP or MMN. Sixteen patients responded to ivIg therapy; they were treated for more than 6 months. Two of them had not previously shown any positive response to other immunosuppressive treatments. Response to ivIg therapy could be observed even after a long disease duration (maximum of 19.5 years). All 16 therapy responders now have no or only mild clinical symptoms. Treatment could eventually be completely stopped in 6 patients; they have now been in complete remission without therapy for a maximum of 63 months. Ten patients still receive regular ivIg infusions in different dosages. No severe side effects were observed in the whole group. IvIg therapy is an effective, safe and easily applicable treatment regimen even in the long-term course of CIDP and MMN.

Adolescent↗
PubMed1996

Mosaicism for the Charcot-Marie-Tooth disease type 1A duplication suggests somatic reversion.

A female patient with clinical signs and symptoms of a demyelinating neuropathy was shown to have a duplication of the 1.5-Mb region on chromosome 17p11.2, typical of the great majority of cases of Charcot-Marie-Tooth disease type 1A (CMT1A). However, analysis of DNA extracted from peripheral blood revealed a 2:2.4 instead of the usual 2:3 ratio between the 7.8- and 6.0-kb EcoRI fragments in the proximal and distal repetitive extragenic palindromic (REP) elements of CMT1A. Detection of a 3.2-kb EcoRI/SacI kb junction fragment with probe pLR7.8 confirmed the CMT1A duplication. The dosage of this junction fragment, compared with a 2.8-kb EcoRI/SacI fragment of the proximal REP elements of CMT1A, was 2:0.58 instead of the expected 2:1 dosage for heterozygous CMT1A duplications. We hypothesized that the lower dosages of these restriction fragments specific for the CMT1A duplication were due to mosaicism; this was confirmed by fluorescence in situ hybridization analysis with the D17S122-specific probe pVAW409R1. In peripheral blood lymphocytes the percentage of interphase nuclei with a duplication in 17p11.2 was 49%. In interphase nuclei extracted from buccal mucosa, hair-root cells or paraffin-embedded nervous tissue the duplication was detectable in 51%, 66% and 74%, respectively. This is the first report of mosaicism in a patient with a CMT1A duplication identified by three different and independent techniques.

Adult↗