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Dirk Dressler

Publications and source records attributed to Dirk Dressler.

At least 19 recordsLinked to original sources
PubMed2007

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.

Adult↗
PubMed2005

Sonographic discrimination of dementia with Lewy bodies and Parkinson's disease with dementia.

OBJECTIVE: To study the use of transcranial sonography (TCS) in discriminating between patients with dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD). METHODS: Fourteen patients with DLB, 31 with PDD and 73 with PD without dementia (PDnD) were studied with TCS. RESULTS: All assessable patients with DLB, 97% with PDD, and 94% with PDnD showed at least unilateral hyperechogenicity of substantia nigra (SN). However, bilateral marked SN hyperechogenicity was present in 80% of DLB patients but only in one third of PDD and PDnD patients, and was associated with younger age at disease onset in PD but not in DLB. An asymmetry index > or = 1.15 of bilateral SN echogenic sizes, estimated by division of larger size by smaller size, was found in 69% of PDD patients but only 20% of DLB patients. Combination of SN echogenic sizes, asymmetry indices and onset age discriminated PDD from DLB with a sensitivity of 96%, a specificity of 80% and a positive predictive value of 93%. TCS of brainstem raphe, thalami, lenticular nuclei, caudate nuclei and ventricle widths did not discriminate between DLB and PDD. Compared with PDnD patients, DLB and PDD patients exhibited significantly larger widths of third ventricle and of frontal horns. In PDD patients, scores on the Unified Parkinson's Disease Rating Scale correlated with widths of third ventricle and of frontal horns. CONCLUSIONS: SN hyperechogenicity is typical for PDD and DLB. However, size, asymmetry and relation of SN hyperechogenicity to age at disease onset discriminate PDD from DLB.

Adult↗
PubMed2005

Botulinum toxin: mechanisms of action.

This review describes therapeutically relevant mechanisms of action of botulinum toxin (BT). BT's molecular mode of action includes extracellular binding to glycoproteine structures on cholinergic nerve terminals and intracellular blockade of the acetylcholine secretion. BT affects the spinal stretch reflex by blockade of intrafusal muscle fibres with consecutive reduction of Ia/II afferent signals and muscle tone without affecting muscle strength (reflex inhibition). This mechanism allows for antidystonic effects not only caused by target muscle paresis. BT also blocks efferent autonomic fibres to smooth muscles and to exocrine glands. Direct central nervous system effects are not observed, since BT does not cross the blood-brain-barrier and since it is inactivated during its retrograde axonal transport. Indirect central nervous system effects include reflex inhibition, normalisation of reciprocal inhibition, intracortical inhibition and somatosensory evoked potentials. Reduction of formalin-induced pain suggests direct analgesic BT effects possibly mediated through blockade of substance P, glutamate and calcitonin gene related peptide.

Anti-Dyskinesia Agents↗
PubMed2005

Botulinum toxin type B de novo therapy of cervical dystonia: frequency of antibody induced therapy failure.

Botulinum toxin induced therapy failure type B antibody (BT-B, BT-B-AB) has so far only been reported after previous formation of antibodies against botulinum toxin type A (BT-A, BTA- AB). We wanted to explore the risk of BT-B-AB-induced therapy failure in patients who were exposed to botulinum toxin for the first time. For this purpose we followed nine patients with cervical dystonia receiving BT-B (NeuroBloc/Myo- Bloc, Elan Pharmaceuticals) in a dose of 11435 +/- 2977MU during 4.9 +/- 3.0 injection series. All patients showed a satisfactory initial therapeutic response as documented by a Toronto Western Spasmodic Torticollis Rating Scale score reduction from 17.7 +/- 9.4 to 5.3 +/- 4.8 and an overall subjective improvement of 56.1 +/- 28.3%. Seven patients experienced systemic anticholinergic side effects. Five patients had stable therapeutic responses over subsequent injection series. Four patients experienced complete therapy failure with BT-B-AB titres in excess of 10 mU/ml on the mouse diaphragm assay. Doubling the last effective BT-B dose produced neither therapeutic effects nor side effects. Subsequent applications of botulinum toxin type A produced a continued therapeutic response in one patient and complete therapy failure in the other.Despite the small sample size a frequency of 44 % indicates a high risk for BT-B-AB-induced complete therapy failure. The high amount of neurotoxin administered when NeuroBloc/MyoBloc is used might be a contributory factor. Further prospective comparative studies are necessary to monitor the frequency and time course of BT-B-AB formation.

Adult↗
PubMed2005

Botulinum toxin: mechanisms of action.

Botulinum toxin (BT) has been perceived as a lethal threat for many centuries. In the early 1980s, this perception completely changed when BT's therapeutic potential suddenly became apparent. We wish to give an overview over BT's mechanisms of action relevant for understanding its therapeutic use. BT's molecular mode of action includes extracellular binding to glycoprotein structures on cholinergic nerve terminals and intracellular blockade of the acetylcholine secretion. BT affects the spinal stretch reflex by blockade of intrafusal muscle fibres with consecutive reduction of Ia/II afferent signals and muscle tone without affecting muscle strength (reflex inhibition). This mechanism allows for antidystonic effects not only caused by target muscle paresis. BT also blocks efferent autonomic fibres to smooth muscles and to exocrine glands. Direct central nervous system effects are not observed, since BT does not cross the blood-brain barrier and since it is inactivated during its retrograde axonal transport. Indirect central nervous system effects include reflex inhibition, normalisation of reciprocal inhibition, intracortical inhibition and somatosensory evoked potentials. Reduction of formalin-induced pain suggests direct analgesic BT effects possibly mediated by blockade of substance P, glutamate and calcitonin gene-related peptide.

Animals↗
PubMed2005

Mouse diaphragm assay for detection of antibodies against botulinum toxin type B.

With the advent of a commercial preparation of botulinum toxin type B (BT-B) for treatment of cervical dystonia detection of antibodies against BT-B (BT-B-AB) becomes necessary. For this purpose, we carried out a mouse diaphragm assay (MDA) by continuous measurement of the twitch force of a mouse hemidiaphragm preparation elicited by electric stimulation of its phrenic nerve. After exposing the preparation to BT-B 3 ng/ml the time to half-maximal twitch force reduction (paralysis time [PT]) was 69 +/- 4 min (n = 25). Addition of sera from patients with antibodies against BT-A produced a PT of 68 +/- 5 min (n = 24), whereas addition of sera from controls with antibodies against tetanus toxoid produced a PT of 67 +/- 6 min (n = 30). When defined amounts of BT-B-AB were added to the MDA, PT was prolonged. This prolongation was correlated closely to the amount of BT-B-AB added, thus producing a calibration curve. The threshold for BT-B-AB detection was 0.4 mU/ml. When sera from 7 patients (4 women, 3 men; age 50.6 +/- 14.2 years) with cervical dystonia (Toronto Western Spasmodic Torticollis Rating Scale score, 18.9 +/- 2.9) and complete secondary failure of BT-B therapy (NeuroBloc; Elan Pharmaceuticals, Shannon, Ireland; 12,229 +/- 2,601 MU/injection series, 1.86 +/- 0.69 injection series before complete secondary therapy failure; 100.4 +/- 15.8 days between injection series with normal therapeutic effect) were tested, BT-B-AB titers of more than 10 mU/ml were found in all of them. The MDA can be used to measure neutralizing BT-B-AB titers quantitatively and with adequate sensitivity and specificity. Further studies are necessary to understand the role of intermediate BT-B-AB titers in partial BT-B therapy failure.

Animals↗
PubMed2005

Tonic contractions of the tensor tympani muscle: a key to some non-specific middle ear symptoms? Hypothesis and data from temporal bone experiments.

CONCLUSIONS: The results of this study show that in clinical practice it will not be easy to diagnose tonic contractions of the tensor tympani muscle and only a combination of findings will be helpful. Based on these experimental results a clinical study will be started which should clarify the diagnostic relevance of indicators of tonic tensor muscle contractions. OBJECTIVES: There are indications from the literature and from personal experience that tonic contractions of the tensor tympani muscle may play a role in some ear symptoms, such as fullness, certain cases of tinnitus, slight hearing loss or Ménière's disease-like findings. In order to prove this theory we looked for indicators, either visual or functional, to help clinically diagnose the functional state of the muscle, particularly its tonic contraction. MATERIAL AND METHODS: Experiments simulating tensor contractions were carried out on temporal bone specimens. Traction was applied either to the isolated muscle, to its tendon or to the malleus neck. Effects were observed either visually via an endoscope or by impedance audiometry using multiple-frequency tympanometry. RESULTS: During simulated tensor traction the aspect of the tympanic membrane changed slightly, i.e. there was some inward movement of the umbo. However, such effects were only identifiable during the pulling action or by directly comparing the "contracted" and "relaxed" states. Tympanometry revealed a decrease in the peak amplitudes and a shift in the middle ear resonance towards higher frequencies during contractions.

Acoustic Impedance Tests↗
PubMed2005

Mutations in the transketolase-like gene TKTL1: clinical implications for neurodegenerative diseases, diabetes and cancer.

Transketolase proteins or transketolase enzyme activities have been related to neurodegenerative diseases, diabetes, and cancer. Transketolase enzyme variants and reduced transketolase enzyme activities are present in patients with the neurodegenerative disease Wernicke-Korsakoff syndrome. In Alzheimer's disease patients transketolase protein variants with different isoelectric points or a proteolytic cleavage leading to small transketolase protein isoforms have been identified. In diabetes mellitus patients reduced transketolase enzyme activities have been detected and the lipid-soluble thiamine derivative benfotiamine activates transketolase enzyme reactions, thereby blocking three major pathways of hyperglycemic damage and preventing diabetic retinopathy. In cancer inhibition of transketolase enzyme reactions suppresses tumor growth and metastasis. All the observed phenomena have been interpreted solely on the basis of a single transketolase gene (TKT) encoding a single transketolase enzyme. No mutations have been identified so far in TKT transketolase explaining the altered transketolase proteins or transketolase enzyme activities found in neurodegenerative diseases, diabetes and cancer. We demonstrate the presence of a second transketolase enzyme (TKTL1) in humans. During the evolution of the vertebrate genome, mutations in this transketolase gene (TKTL1) have led to tissue-specific transcripts different in size, which encode an enzymatically active transketolase protein as well as different smaller protein isoforms. The mutations within the TKTL1 gene caused a mutant transketolase enzyme with an altered substrate specificity and reaction modus. Here we characterize the TKTL1 gene and its encoded TKTL1 protein(s) and discuss the medical and clinical implications of this mutated transketolase. We furthermore postulate a novel metabolic concept for the understanding, prevention and therapy of neurodegenerative diseases, diabetes and cancer.

Diabetes Mellitus↗
PubMed2004

Antibody-induced failure of botulinum toxin type B therapy in de novo patients.

Botulinum toxin type B (BT-B) therapy failure due to formation of botulinum toxin type B antibodies (BT-B-AB) has only been reported in patients with botulinum toxin type A antibodies (BT-A-AB). We are reporting BT-B-AB-induced therapy failure in 2 patients with no previous exposure to botulinum toxin. In patient 1 complete therapy failure occurred after a single exposure to 14,400 mouse units (MU) BT-B (NeuroBloc). The mouse diaphragm assay (MDA) revealed a BT-B-AB titre in excess of 10 mU/ml. Doubling the BT-B dose did not elicit any effects. Application of 360 MU BT-A (Botox) produced the original therapeutic effect, but the second BT-A application was followed by partial and the third by complete therapy failure. Doubling the BT-A dose did not elicit any effects. MDA testing showed a BT-A-AB titre in excess of 10 mU/ml. In patient 2 a single exposure to 7,200 MU BT-B lead to a complete therapy failure. MDA testing revealed a BT-B-AB titre in excess of 10 mU/ml. Doubling the BT-B dose did not elicit any effects. Application of 180 MU BT-A (Botox) produced the original response on 3 consecutive applications. Antibody formation can occur after a single exposure to botulinum toxin. However, this is highly unusual. Since therapy failure occurred after the first-ever botulinum toxin exposure, short intervals between injections and use of booster injections can be excluded as causes for BT-B-AB formation in both patients. A more likely cause may be the substantially higher amount of antigenic protein administered in BT-B therapy compared to BT-A therapy. Further studies are necessary to compare the incidence of antibody formation in BT-B and BT-A therapy.

Adult↗
PubMed2004

Clinical presentation and management of antibody-induced failure of botulinum toxin therapy.

Therapy with botulinum toxin (BT) can fail due to numerous reasons, including failure due to formation of antibodies against BT (BT-AB, AB-TF). AB-TF is a secondary therapy failure, i.e. it occurs during the course of an ongoing BT therapy. It can be subjective or objective, temporary or permanent, and partial or complete. Complete AB-TF is usually preceded by injection series with partial AB-TF in which the therapeutic effect is reduced in its intensity and duration. AB-TF usually occurs within 2 or 3 years after initiation of BT therapy. After 4 years it is rare. BT-AB are neutralising or blocking by definition, i.e. they are directly interfering with BT's biological mechanism of action. Non-neutralizing or non-blocking antibodies occur. BT-AB can be detected by the mouse diaphragm assay, the mouse protection assay, and by patient-based tests such as the sternocleidomastoid test, the extensor digitorum brevis test, and the frowning test. Enzyme-linked immunosorbent assays (ELISA) have a low specificity and a low sensitivity for detection of BT-AB. BT-AB titres drop spontaneously after cessation of BT therapy but latencies are too long to be compatible with an effective BT therapy. BT dosage increase can be successful to overcome AB-TF when AB-TF is partial and when BT-AB titres are low. Usage of alternative BT type A preparations fail to overcome AB-TF. Alternative BT types, such as BT type B and BT type F, are initially successful in AB-TF, but stimulate formation of antibodies against the alternative BT types after few applications. BT-AB reduction with immunosuppressants and inactivation of BT-AB by intravenous immunoglobuline application has not yet been achieved. Extraction of BT-AB by plasmapheresis and immunoadsorption is possible but is associated with substantial logistic problems. Prevention of BT-AB formation, therefore, is of paramount importance. Identified risk factors for BT-AB formation must be taken into account when BT therapy is planned. The most interesting perspective seems to be the development of new BT preparations with reduced antigenicity.

Action Potentials↗
PubMed2004

Lack of mutations in the epsilon-sarcoglycan gene in patients with different subtypes of primary dystonias.

Primary dystonias represent a clinically and genetically heterogeneous group of movement disorders. Mutations in the epsilon-sarcoglycan (SGCE) gene have been found recently to cause myoclonus-dystonia (MD). Considerable clinical variation of SGCE mutation carriers leads to the hypothesis that mutations in the SGCE gene might also be relevant for other subtypes of dystonias. To determine the contribution of mutations in the SGCE gene in patients with different subtypes of dystonias, we analyzed the coding sequence of the SGCE gene in a group of 296 patients with a clinical phenotype of primary dystonia and in 2 patients with a clinical phenotype of myoclonus-dystonia. Patients with mutations in the DYT1 gene were excluded. We could not detect a mutation in the SGCE gene in any of the 298 patients. Our results suggest that mutations in the SGCE gene cannot be held responsible for other subtypes of primary dystonia.

Adult↗
PubMed2004

Brain parenchyma sonography detects preclinical parkinsonism.

Substantia nigra (SN) hyperechogenicity on brain parenchyma sonography (BPS) is highly characteristic for idiopathic PD. We studied 7 symptomatic and 7 asymptomatic parkin mutation carriers (PMC) from a large kindred with adult-onset parkinsonism. BPS revealed larger SN echogenic sizes in PMC with parkin mutations on both alleles (homozygous, compound-heterozygous), compared to PMC with only one mutated allele (Mann-Whitney U test, P = 0.007). In symptomatic PMC, larger SN echogenic size was correlated with younger age at onset of the disease (Spearman rank correlation, Rho = -0.937, P = 0.002) but not with age, disease duration, or disease severity. BPS demonstrated SN hyperechogenicity, in concordance with abnormal nigrostriatal (18)F-dopa positron emission tomography (PET), in all symptomatic and 3 asymptomatic PMC. In 2 asymptomatic PMC, PET and BPS were normal. However, in another 2 asymptomatic PET-normal PMC, SN hyperechogenicity could be detected. Data suggest SN hyperechogenicity as an early marker to detect preclinical parkinsonism.

Adult↗
PubMed2004

Mutation at the SCA17 locus is not a common cause of primary dystonia.

Spinocerebellar ataxia type 17 (SCA17) is a dominant progressive neurodegenerative disorder, caused by a triplet repeat expansion within the TATA-binding protein. As well as ataxia and dementia, Parkinsonism and dystonia are common in SCA17. In some pedigrees focal dystonia in the absence of ataxia has been described as a main clinical feature. To evaluate the relevance of SCA17 mutations for primary dystonia, we examined the TBP repeat expansion in a series of 288 patients with different subtypes of primary torsion dystonia. We did not find any repeat sizes in the pathogenic range. We conclude that the SCA17 repeat expansion is not a common cause of familial and sporadic dystonia.

Adult↗
PubMed2003

Frequency and phenotypic variability of the GAG deletion of the DYT1 gene in an unselected group of patients with dystonia.

BACKGROUND: Dystonia is a clinically and genetically heterogeneous movement disorder characterized by sustained muscle contractions affecting one or more sites of the body, frequently causing twisting and repetitive movements or abnormal postures. A 3-base pair (GAG) deletion in the DYT1 gene is held responsible for most cases of early-onset primary generalized dystonia in the Ashkenazi Jewish population as well as in non-Jewish patients. OBJECTIVES: To investigate the prevalence of the GAG deletion in the DYT1 gene and the phenotypic variability in the general population by testing patients with different subtypes of dystonia from 4 different movement disorder outpatient clinics in Germany. METHODS: Two hundred fifty-six patients were tested for the GAG deletion mutation in the DYT1 gene by means of published primers and polymerase chain reaction amplification to determine GAG deletion status. RESULTS: Six of the 256 patients did carry the GAG-deletion in the DYT1 gene. However, only 2 of the 6 mutation carriers presented with what is thought to represent classic features of early-onset primary generalized dystonia. The DYT1 mutation was also detected in 2 patients with multifocal dystonia, 1 of them presenting with involvement of cranial and cervical muscles, and in 2 patients with writer's cramp of both hands with only slight progression. Our findings demonstrate that the mutation may be associated with not only generalized but also segmental and multifocal forms of dystonia. CONCLUSIONS: Our data underline the wide range of phenotypic variability of the DYT1 mutation. A priori prediction of the mutation carrier status in dystonic patients and genetic counseling of affected families with respect to the clinical manifestation may prove difficult.

Base Pairing↗