Publications (20)74.55 Total impact
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Article: Long-term course of substantia nigra hyperechogenicity in Parkinson's disease.
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ABSTRACT: A hyperechogenicity of the (SN+) in transcranial sonography corroborates the diagnosis of idiopathic Parkinson's disease (iPD). Although it is thought to represent a biomarker of the disease that is independent of disease severity and progression, differing results have been reported describing a positive correlation of the size and advancing clinical stage. In 50 parkinsonian patients, transcranial ultrasound and clinical examination was performed twice with a mean time interval of 6.4 years. SN+ did not change in size significantly between the first and second examination, whereas clinical parkinsonian symptoms-as determined by the motor part of the UPDRS-significantly worsened (P < 0.001). We found a highly significant intraindividual correlation in SN+ sizes between both examinations (P < 0.001). The size of SN+ did not correlate with the UPDRS part III at the time of first or second ultrasound examination. Progression of motor symptoms between the first and second investigation did not correlate with the size of SN+ at baseline. Furthermore, even in the subgroup of patients with an interval of ≥8 years between examinations, there was no significant change in SN+ size. SN+ represents a largely stable biomarker in iPD and does not reflect disease progression. The size of SN+ does not predict the further course of the disease. © 2012 Movement Disorder Society.Movement Disorders 10/2012; · 4.51 Impact Factor -
Article: Response of Toll-like receptors in experimental Guillain-Barré syndrome: a kinetic analysis.
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ABSTRACT: Guillain-Barré syndrome (GBS) is an autoimmune disorder caused by the interaction between cellular and humoral immune responses in the peripheral nervous system. Toll-like receptors (TLRs) are key players in innate and have regulatory functions in adaptive immunity. In this study, we systematically examined expression patterns of TLRs in sciatic nerve and lymphoid organs during the disease course of murine experimental autoimmune neuritis and in blood from Guillain-Barré patients. A kinetic response pattern was identified, characterized by a pronounced up-regulation of TLR2, 6 and 11 on T cells and TLR4 and 6 on APCs, while TLR1 expression was decreased. Moreover, an enhanced expression of the disease promoting cytokine Interleukin-(IL)17A was detected. Additional analysis of GBS patients revealed an up-regulation of TLR2, TLR4 and TLR6 mRNA, negatively correlated with disease severity. This first systematic analysis of TLR expression pattern may contribute to elucidating the role of TLRs in GBS pathophysiology.Neuroscience Letters 05/2012; 518(2):154-60. · 2.11 Impact Factor -
Article: Enlarged substantia nigra hyperechogenicity and risk for Parkinson disease: a 37-month 3-center study of 1847 older persons.
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ABSTRACT: To evaluate whether enlarged substantia nigra hyperechogenicity (SN+) is associated with an increased risk for Parkinson disease (PD) in a healthy elderly population. Longitudinal 3-center observational study with 37 months of prospective follow-up. Individuals 50 years or older without evidence of PD or any other neurodegenerative disease. Of 1847 participants who underwent a full medical history, neurological assessment, and transcranial sonography at baseline, 1535 could undergo reassessment. Incidence of new-onset PD in relation to baseline transcranial sonography status. There were 11 cases of incident PD during the follow-up period. In participants with SN+ at baseline, the relative risk for incident PD was 17.37 (95% confidence interval, 3.71-81.34) times higher compared with normoechogenic participants. In this prospective study, we demonstrate for the first time a highly increased risk for PD in elderly individuals with SN+. Transcranial sonography of the midbrain may therefore be a promising primary screening procedure to define a risk population for imminent PD.Archives of neurology 07/2011; 68(7):932-7. · 6.31 Impact Factor -
Article: Myocardial MIBG scintigraphy may predict the course of motor symptoms in Parkinson's disease.
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ABSTRACT: The metaiodobenzylguanidine (MIBG) scintigraphy is a well established nuclear medicine method to support the clinical diagnosis of Parkinson's disease. In this study we examined the predictive value of the MIBG scintigraphy concerning the severity and progression of the parkinsonian motor symptoms. This study included 40 patients with idiopathic Parkinson's disease (age 56 ± 9 years, Hoehn and Yahr stage 1.4 ± 0.7, mean ± standard deviation). All patients underwent a baseline visit and a follow-up visit 3-8 years (5.3 ± 1.6 years) after the baseline visit. (123)I-MIBG scintigraphy was performed only once at the baseline visit. At both visits the motor symptoms bradykinesia, rigidity, resting tremor, postural tremor and axial symptoms were quantified by means of the motor part of the Unified Parkinson's disease rating scale. The myocardial MIBG uptake correlated significantly with the annual progress of rigidity (r=-0.41, p<0.05; Pearson's correlation) and axial symptoms (r=-0.49, p<0.01). There was no significant correlation (p>0.05) between the initial myocardial MIBG uptake and the annual progress of the other motor symptoms. The MIBG scintigraphy may predict the velocity of progress of rigidity and axial symptoms in the following 3-8 years. Such a prediction is not possible for the other motor symptoms resting tremor, postural tremor and bradykinesia.Parkinsonism & Related Disorders 03/2011; 17(5):372-5. · 3.80 Impact Factor -
Article: Doxepin concentrations in plasma and cerebrospinal fluid.
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ABSTRACT: Doxepin--like other antidepressant drugs (ADs)--shows a variable antidepressant effect in clinical practice. The cause for this variability is as yet unclear; however, pharmacokinetic factors such as the variable permeability of doxepin into the cerebrospinal fluid (CSF), may contribute to the difference in therapeutic efficacy. We measured and correlated the concentration of doxepin and its active metabolite nordoxepin in both the plasma and CSF. Plasma and CSF samples were taken simultaneously from 21 patients who were treated with doxepin due to different clinical indications. The plasma concentration of both doxepin and nordoxepin correlated significantly with the oral dosage of doxepin (doxepin: r = +0.66, p < 0.001; nordoxepin: r = +0.78, p < 0.0001; Spearman's correlation). Furthermore, we found significant correlations between the plasma and CSF concentrations of both doxepin (r = +0.71; p < 0.001; Pearson's correlation) and nordoxepin (r = +0.74; p < 0.001). These highly significant correlations between the plasma and CSF concentrations indicate a constant CSF permeability of doxepin and its active metabolite nordoxepin.Acta Neurovegetativa 02/2011; 118(4):641-5. · 2.73 Impact Factor -
Article: Diagnostic and Pathophysiological Impact of Myocardial MIBG Scintigraphy in Parkinson's Disease.
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ABSTRACT: Myocardial MIBG scintigraphy is established in the diagnosis and differential diagnosis of Parkinson's disease (PD). Numerous studies address the pathophysiological impact of myocardial MIBG scintigraphy: the myocardial MIBG uptake correlates with the clinical phenotype of PD; the background of this phenomenon is unclear. Furthermore MIBG scintigraphy enables to study the extracranial Lewy body type-degeneration. In combination with cerebral dopamine transporter imaging, MIBG scintigraphy allows to correlate cerebral and extracranial Lewy body type-degeneration in PD.Parkinson's disease. 01/2010; 2010:295346. -
Article: Randomized, double-blind, placebo-controlled trial on symptomatic effects of coenzyme Q(10) in Parkinson disease.
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ABSTRACT: Major hallmarks in the pathophysiology of Parkinson disease are cellular energy depletion and oxidative stress leading to cellular dysfunction and death. Coenzyme Q(10) (CoQ(10)) is an electron acceptor bridging mitochondrial complexes I and II/III and a potent antioxidant that consistently partially recovers the function of dopaminergic neurons. To determine whether nanoparticular CoQ(10) is safe and displays symptomatic effects in patients with midstage Parkinson disease without motor fluctuations. Multicenter, randomized, double-blind, placebo-controlled, stratified, parallel-group, single-dose trial. Academic and nonacademic movement disorder clinics. One hundred thirty-one patients with Parkinson disease without motor fluctuations and a stable antiparkinsonian treatment. Intervention Random assignment to placebo or nanoparticular CoQ(10) (100 mg 3 times a day) for a treatment period of 3 months. Stratification criterion was levodopa treatment. The subjects underwent evaluation with the Unified Parkinson's Disease Rating Scale (UPDRS) at each visit on a monthly basis. The primary outcome variable was the change of the sum score of the UPDRS parts II and III between the baseline and 3-month visits. One hundred thirty-one subjects were randomized according to the protocol. The mean changes of the sum UPDRS parts II/III score were -3.69 for the placebo group and -3.33 for the CoQ(10) group (P = .82). Statistical analysis according to the stratification did not result in significant changes of the primary outcome variable. No secondary outcome measure showed a significant change between the placebo group and the CoQ(10) group. The frequency and quality of adverse events were similar in both treatment groups. Nanoparticular CoQ(10) at a dosage of 300 mg/d is safe and well tolerated and leads to plasma levels similar to 1200 mg/d of standard formulations. Add-on CoQ(10) does not display symptomatic effects in midstage Parkinson disease.Archives of Neurology 08/2007; 64(7):938-44. · 7.58 Impact Factor -
Article: Myocardial sympathetic degeneration correlates with clinical phenotype of Parkinson's disease.
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ABSTRACT: In idiopathic Parkinson's disease (PD), different clinical subtypes are distinguished due to predominant motor symptoms: a tremor-dominant type (TDT), an akinetic rigid type (ART), and a mixed type (MT). We compared myocardial sympathetic innervation, measured by MIBG scintigraphy, in different subtypes of PD at early and advanced stages of PD. We applied MIBG scintigraphy in 102 patients with PD. About 57 patients were at Hoehn and Yahr (H&Y) stage 1, 22 at H&Y stage 2, and 23 at H&Y stages 3 and 4. For quantification of myocardial MIBG uptake, the heart-to-mediastinum (H/M) count-ratio was calculated. At all H&Y stages, myocardial MIBG uptake was significantly higher in TDT patients than in ART or MT patients (P < 0.05; ANOVA). Furthermore, at each H&Y stage, myocardial MIBG uptake correlated significantly with severity of hypokinesia (P < 0.05; Spearman's correlation) and rigidity (P < 0.05), but not with severity of resting or postural tremor. The significant correlation between myocardial sympathetic degeneration and severity of hypokinesia and rigidity suggests that myocardial sympathetic degeneration and hypokinetic-rigid symptoms develop in a closely coupled manner in early as well as advanced PD. No such correlation can be found between myocardial sympathetic degeneration and parkinsonian tremor.Movement Disorders 05/2007; 22(7):1004-8. · 4.51 Impact Factor -
Article: Cerebral and Extracranial Neurodegeneration are Strongly Coupled in Parkinson's Disease.
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ABSTRACT: In idiopathic Parkinson's disease (PD), a generalized Lewy body type-degeneration in the brain as well as extracranial organs was identified. It is unclear, whether cerebral and extracranial Lewy body type-degeneration in PD are coupled or not. To address this question, cerebral [(123)I]FP-CIT SPECT - to quantify cerebral nigrostriatal dopaminergic degeneration - and myocardial [(123)I]MIBG scintigraphy - to quantify extracranial myocardial sympathetic degeneration - were performed in 95 PD patients and 20 healthy controls. At each Hoehn and Yahr stage separately, myocardial MIBG uptake correlated significantly with striatal FP-CIT uptake. No such correlation was found in the controls. Cerebral and extracranial Lewy body type-degeneration in PD do not develop independently from each other but develop in a strongly coupled manner. Obviously cerebral and extracranial changes are driven by at least similar pathomechanisms. Our findings in controls contradict a physiological correlation between nigrostriatal dopaminergic and myocardial sympathetic function.The Open Neurology Journal 02/2007; 1:1-4. -
Article: Early diagnosis of Parkinson’s disease
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ABSTRACT: The clinical methods of olfactory testing and color discrimination as well as apparative methods such as transcranial ultrasound, dopamine transporter imaging and MIBG scintigraphy reveal a high sensitivity concerning the diagnosis of idiopathic Parkinson’s disease (PD). The specificity of the presented methods, in particular of the dopamine transporter imaging—seems to be limited. All these methods and primarily their combination allow the detection of PD in early and—probably—preclinical stages. This requires sufficient therapeutic strategies to prevent and treat preclinical and early PD.Journal of Neurology 08/2006; 253:iv2-iv7. · 3.47 Impact Factor -
Article: Early diagnosis of Parkinson's disease.
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ABSTRACT: The clinical methods of olfactory testing and color discrimination as well as apparative methods such as transcranial ultrasound, dopamine transporter imaging and MIBG scintigraphy reveal a high sensitivity concerning the diagnosis of idiopathic Parkinson's disease (PD). The specificity of the presented methods, in particular of the dopamine transporter imaging--seems to be limited. All these methods and primarily their combination allow the detection of PD in early and--probably--preclinical stages. This requires sufficient therapeutic strategies to prevent and treat preclinical and early PD.Journal of Neurology 08/2006; 253 Suppl 4:IV2-7. · 3.47 Impact Factor -
Article: Transcranial sonography and [123I]FP-CIT SPECT disclose complementary aspects of Parkinson's disease.
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ABSTRACT: Hyperechogenic signal of substantia nigra (SN) in transcranial sonography (TCS) and reduced striatal uptake in FP-CIT SPECT are common findings in idiopathic Parkinson's disease (PD). But so far it is unknown whether the extent of SN hyperechogenicity represents a correlate for the degeneration of presynaptic dopaminergic neurons in PD. We performed TCS and 123I-labelled N-(3-fluoropropyl)-2ss-carbomethoxy-3ss-(4-iodophenyl)nortropane ([123I]FP-CIT) SPECT in 53 patients with PD. Striatal FP-CIT uptake was quantified by measuring the striatal/posterior lobe binding of [123I]FP-CIT. SN echogenicity was quantified by planimetric measurement of the maximum extension of hyperechogenic signals. We found no correlation between striatal FP-CIT uptake and echogenicity of the SN, neither contralateral to the clinically more affected body side (r = +0.08, P = 0.57; Pearson's correlation) nor ipsilateral (r = +0.01; P = 0.92). Our data show that the extent of SN hyperechogenicity does not correlate with the degeneration of presynaptic dopaminergic nerve terminals. Obviously SN hyperechogenicity and degeneration of presynaptic dopaminergic nerve terminals exist independently from each other and may be based on different pathomechanisms.Brain 06/2006; 129(Pt 5):1188-93. · 9.46 Impact Factor -
Article: Orthostatic tremor during modification of standing.
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ABSTRACT: Primary orthostatic tremor (OT) occurs only during standing. We studied whether modification of the condition standing influences OT. In seven patients with OT, surface EMG was recorded from both tibialis anterior and gastrocnemius muscles during two maneuvers: relief, whereby the patient was gradually lifted by a crane, and tilting, whereby the patient was tilted by a tilting table to positions of 90 degrees (upright standing), 45 degrees (diagonal position), and 0 degrees (lying position). We determined the parameters tremor frequency, tremor intensity, coherence, and phase shift between the different muscles. Relief did not influence OT. In contrast, tilting modified significantly tremor intensity and phase shifts; tremor frequencies and coherences were not influenced. We chose both these maneuvers because of their different impact on the standing condition: relief modifies the factors afferent input and muscle forcing but not the factor postural set, whereas tilting modifies all three factors. The fact that tilting modifies OT, whereas relief does not, suggests an important role of postural set in OT generation. Afferent input and muscle forcing seem to play less important role.Movement Disorders 03/2006; 21(2):173-8. · 4.51 Impact Factor -
Article: Functional relevance of ceruloplasmin mutations in Parkinson's disease.
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ABSTRACT: Increased iron levels of the substantia nigra and the discovery of ceruloplasmin mutations in patients with Parkinson's disease (PD) imply impaired iron metabolism in this neurodegenerative disorder. Ceruloplasmin has ferroxidase activity oxidizing iron(II) to iron(III). In the present study, we analyzed the amount of ceruloplasmin, iron, ferritin, and transferrin and the ceruloplasmin ferroxidase activity in serum of patients with the diagnosis of PD carrying the ceruloplasmin mutations I63T, D544E, and R793H. The impact of these missense mutations on the biosynthesis of holo-ceruloplasmin was investigated in cell culture experiments. Functional relevance was found for the ceruloplasmin mutations I63T and D544E. In vivo, the I63T mutation resulted in half the normal ceruloplasmin concentration and markedly reduced ferroxidase activity in serum from a heteroallelic PD patient. In cell culture, the I63T glycosylphosphatidylinositol (GPI)-linked ceruloplasmin isoform was retained in the endoplasmatic reticulum of human embryonic kidney cells. Furthermore, the D544E polymorphism resulted in significantly reduced serum ceruloplasmin levels and ferroxidase activity in heteroallelic patients and in expression of mainly apo-ceruloplasmin in cell culture. Our studies indicate that altered activity of ceruloplasmin may present a vulnerability factor for iron induced oxidative stress in PD.The FASEB Journal 12/2005; 19(13):1851-3. · 5.71 Impact Factor -
Article: FP-CIT and MIBG scintigraphy in early Parkinson's disease.
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ABSTRACT: Methods provided by nuclear medicine may be helpful in diagnosis of Parkinson's disease (PD). For that purpose, the sensitivity of iodine-123 metaiodobenzylguanidine ([123I]MIBG) scintigraphy and [123I]FP-CIT single photon emission computed tomography (SPECT) was studied in patients with PD onset (Hoehn and Yahr Stage 1). Cerebral [123I]FP-CIT and cardiac [123I]MIBG scintigraphy were carried out in 18 patients with idiopathic Parkinson's disease, according to Hoehn and Yahr Stage 1. For quantification purposes, we calculated the striatum/posterior lobe binding of FP-CIT and the heart-to-mediastinum (H/M) count ratio regarding MIBG scintigraphy. In 15 of 18 patients, we observed markedly reduced or asymmetric striatal FP-CIT tracer accumulation. FP-CIT binding of the affected striatum was significantly lower as compared with that of the unaffected side. Striatal FP-CIT binding correlated significantly with the motor part of the Unified Parkinson's disease rating scale (UPDRS) but not with age, disease duration, or gender. MIBG scintigraphy delivered significant pathological results in 13 of 18 patients. There was no significant correlation between the H/M ratio relating to MIBG scintigraphy and the motor part of UPDRS, age, disease duration, or gender; however, binding of striatal FP-CIT correlated significantly with cardiac MIBG accumulation. According to the clinical criteria, it might be difficult to prove the diagnosis of PD in patients with slight symptoms and in these cases, FP-CIT SPECT and MIBG scintigraphy may contribute to the early diagnosis of PD. In addition, the functional loss of nigrostriatal and cardiac sympathetic neurons seems to be coupled closely.Movement Disorders 06/2005; 20(5):552-61. · 4.51 Impact Factor -
Article: Improvement of upper limb ataxia and intention tremor allowing cessation of thalamic electrostimulation after four years.
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ABSTRACT: A 34-year-old female patient suffering from multiple sclerosis was treated with thalamic electrostimulation for right dominant brachial ataxia and intention tremor. At the end of the fourth year, the energy of the battery of the impulse generator was depleted. However, the patient was able to use her hands without major impairment with the stimulator OFF; due to a stable reduction of the degree of ataxia and intention tremor. The opposite thalamus received an electrode that was never activated because of a permanent thalamotomy effect. Thus, it can be concluded that restoration of function by means of deep brain stimulation might have been beneficial towards achieving a reorganization and stabilization of subcortico-cortical and cerebellar circuitry, supporting the process of self-repair in this patient with a less aggressive course of multiple sclerosis. However, scientific proof has yet to be found. This exceptional observation emphasizes the need for longterm studies.Multiple Sclerosis 01/2005; 10(6):708-10. · 4.26 Impact Factor -
Article: Screening for mutations of the ferritin light and heavy genes in Parkinson's disease patients with hyperechogenicity of the substantia nigra.
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ABSTRACT: Recently, an insertional mutation in the ferritin-L gene was reported in some patients with familial basal ganglia degeneration, which, however, could not be detected in another Parkinson's disease (PD) population. We investigated 186 PD patients, in whom an increased amount of iron of the substantia nigra (SN) was priorly identified by transcranial ultrasound, for mutations of the whole coding region of ferritin-L and ferritin-H by denaturing high-pressure liquid chromatography and subsequent sequencing. In the ferritin-L gene two silent mutations were detected. In the ferritin-H gene the sequence variation 161A-->G was found in one patient but none of the 186 controls. Although functional analysis will show, whether this sequence variation might be causative for single cases of PD, the results indicate that mutations in the ferritin genes are not a common cause for PD with increased levels of iron of the SN.Neuroscience Letters 11/2003; 352(1):53-6. · 2.11 Impact Factor -
Article: Transient dystonia following magnetic resonance imaging in a patient with deep brain stimulation electrodes for the treatment of Parkinson disease. Case report.
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ABSTRACT: Data from previous studies have shown that magnetic resonance (MR) imaging of the head can be performed safely in patients with deep brain stimulators. The authors report on a 73-year-old patient with bilaterally implanted deep brain electrodes for the treatment of Parkinson disease, who exhibited dystonic and partially ballistic movements of the left leg immediately after an MR imaging session. Such dystonic or ballistic movements had not been previously observed in this patient. In the following months, this focal movement disorder resolved completely. This case demonstrates the possible risks of MR imaging in patients with deep brain stimulators.Journal of Neurosurgery 10/2003; 99(4):772-4. · 2.96 Impact Factor -
Article: Influence of proprioceptive input on parkinsonian tremor.
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ABSTRACT: Previous studies have shown a modification of parkinsonian tremor (PT) by proprioceptive input induced by passive joint movements. The authors investigated the impact of electrically evoked proprioceptive input on PT. In eight patients with PT they recorded surface EMG from the opponens pollicis muscle, and forearm extensors and flexors. Rhythmic electrical stimulation was applied to the ipsilateral median nerve at the wrist using a submaximal stimulus intensity and stimulus frequencies between two stimuli per second and five stimuli per second. The tremor frequency did not adapt to the stimulus frequency. Tremor frequency of parkinsonian resting tremor increased significantly in the directly stimulated opponens pollicis muscle (mean +/- standard deviation, 4.35 +/- 0.64 Hz without stimulation versus 4.53 +/- 0.68 Hz with stimulation; P < 0.05, paired t-test), the not directly stimulated forearm muscles (4.90 +/- 0.72 Hz versus 5.18 +/- 0.73 Hz, P < 0.001), and the upper arm muscles (5.13 +/- 0.61 Hz versus 5.36 +/- 0.68 Hz, P < 0.01). Furthermore, the parkinsonian postural tremor accelerated significantly during ipsilateral median nerve stimulation (5.31 +/- 0.99 Hz versus 5.44 +/- 1.03 Hz, P < 0.05). Parkinsonian resting tremor in the forearm muscles also accelerated significantly during ipsilateral ulnar nerve stimulation (4.85 +/- 0.57 Hz versus 5.05 +/- 0.65 Hz, P < 0.05). Contralateral median nerve stimulation had no significant effect. These results suggest a close interaction between proprioceptive input and PT generation.Journal of Clinical Neurophysiology 01/2002; 19(1):84-9. · 1.45 Impact Factor -
Article: [Effect of deep brain stimulation on glottal phonation in patients with Parkinson's disease and multiple sclerosis].
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ABSTRACT: The present study examines the effect of neurostimulatory operations on glottal phonation of 3 parkinsonian patients and 3 patients with multiple sclerosis. With the help of two voice analysis programs (MDVP from Kay Elemetrics and EEG Program by Marasek) for the acoustic and electroglottographic definition of voice characteristics, vowel productions of the patients, which were recorded under two conditions (with and without stimulation), were analysed. In a first step, significantly different intrasubject means in the two conditions indicate the effect of neurostimulation. The strength of the effect differs among subjects, particularly in the case of patients with Parkinson's disease. In a second step, a gender-differentiated comparison of the individual patient's data (recorded with and without stimulation) with a group of normal voice speakers (150 male and 150 female speakers) is carried out. This intersubject comparison proves useful in that it relativizes the results from the intrasubject comparison. It is shown for the parkinsonian patients that stimulation causes a relative deterioration of the glottal cycle, while for the patients with multiple sclerosis a tendency for hyperfunctional phonation is observed. In the latter case, the results suggest the need for long-term monitoring of phonation behaviour during chronic electrical stimulation.Folia Phoniatrica et Logopaedica 55(5):220-32. · 1.12 Impact Factor
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2002–2011
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Universität des Saarlandes
Homburg, Saarland, Germany
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