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Dr Maria Stamelou

Maria Stamelou, MD, PhD

Sobell Department of Motor Neuroscience and Movement Disorders,
UCL Institute of Neurology, London, WC1N 3BG, United Kingdom

Journal articles

Georgia Xiromerisiou, Henry Houlden, Nikolaos Scarmeas, Maria Stamelou, Eleanna Kara, John Hardy, Andrew J Lees, Prasad Korlipara, Patricia Limousin, Reema Paudel, Georgios M Hadjigeorgiou, Kailash P Bhatia (2012)  THAP1 mutations and dystonia phenotypes: Genotype phenotype correlations.   Mov Disord Aug  
Abstract: THAP1 mutations have been shown to be the cause of DYT6. A number of different mutation types and locations in the THAP1 gene have been associated with a range of severity and dystonia phenotypes, but, as yet, it has been difficult to identify clear genotype phenotype patterns. Here, we screened the THAP1 gene in a further series of dystonia cases and evaluated the mutation pathogenicity in this series as well as previously reported mutations to investigate possible phenotype-genotype correlations. THAP1 mutations have been identified throughout the coding region of the gene, with the greatest concentration of variants localized to the THAP1 domain. In the additional cases analyzed here, a further two mutations were found. No obvious, indisputable genotype-phenotype correlation emerged from these data. However, we managed to find a correlation between the pathogenicity of mutations, distribution, and age of onset of dystonia. THAP1 mutations are an important cause of dystonia, but, as yet, no clear genotype-phenotype correlations have been identified. Greater mutation numbers in different populations will be important and mutation-specific functional studies will be essential to identify the pathogenicity of the various THAP1 mutations. © 2012 Movement Disorder Society.
Amit Batla, Maria Stamelou, Kailash P Bhatia (2012)  Treatment of focal dystonia.   Curr Treat Options Neurol 14: 3. 213-229 Jun  
Abstract: OPINION STATEMENT: Dystonia is characterized by repetitive twisting movements or abnormal postures due to involuntary muscle activity. When limited to a single body region it is called focal dystonia. Examples of focal dystonia include cervical dystonia (neck), blepharospasm (eyes), oromandibular dystonia, focal limb dystonia, and spasmodic dysphonia, which are discussed here. Once the diagnosis is established, the therapeutic plan is discussed with the patients. They are informed that there is no cure for dystonia and treatment is symptomatic. The main therapeutic option for treating focal dystonias is botulinum toxin (BoNT). There have been several attempts to characterize the procedure, the type of toxin, dosage, techniques, and combination with physical measures in each of the focal dystonia forms. The general treatment principles are similar. The affected muscles are injected at muscle sites based on evidence and experience using standard dosages based on the type of toxin used. The injections are repeated after 3 to 6 months based on the individual response duration. In the uncommon event of nonresponse with BoNT, the dose and site are reassessed. Oral drug treatment could be considered as an additional option. Once the condition is thought to be medically refractory, the opinion from the deep brain stimulation (DBS) team for the suitability of the patient for DBS is taken. The successful use of DBS in cervical dystonia has led to increased acceptance for trial in other forms of focal dystonias. DBS surgery in focal dystonias other than cervical is, however, still experimental. The patients may be offered the surgery with adequate explanation of the risks and benefits. Patient education and directing the patients towards dystonia support groups and relevant websites that provide scientific information may be useful for long-term compliance and benefit.
Maria Stamelou, Tabish A Saifee, Mark J Edwards, Kailash P Bhatia (2012)  Psychogenic palatal tremor may be underrecognized: Reappraisal of a large series of cases.   Mov Disord 27: 9. 1164-1168 Aug  
Abstract: Palatal tremor is characterized by rhythmic movements of the soft palate and can be essential or symptomatic. Some patients can have palatal movements as a special skill or due to palatal tics. Psychogenic palatal tremor is recognized but rarely reported in the literature.
Maria Stamelou, Giuseppe Plazzi, Elio Lugaresi, Mark J Edwards, Kailash P Bhatia (2012)  The distinct movement disorder in anti-NMDA receptor encephalitis may be related to status dissociatus: A hypothesis.   Mov Disord Jun  
Abstract: The majority of patients with anti-N-methyl-D-aspartate-receptor encephalitis (NMDAE) present a characteristic movement disorder, which consists of complex bilateral stereotyped movements of the arms, with perioral and eye movements, and less frequently involvement of the legs. We have observed striking similarities in the characteristics of the abnormal movements observed in NMDAE and those described in Status Dissociatus, which is characterized by a complete breakdown of state-determining boundaries (wakefulness, REM and NREM sleep) and can result from pathophysiologically diverse disorders (e.g. fatal familial insomnia, delirium tremens, Morvan's syndrome). Here, we suggest that the state of paradoxical responsiveness in which NMDAE patients present these stereotyped movements may be that of Status Dissociatus and discuss the clinical similarities and pathophysiological explanations that support such a suggestion. This hypothesis explains why patients that seem to be unconscious have a movement disorder that is not epileptic and may have management implications, since many patients with NMDAE-related movement disorder are treated with anticonvulsants that may not be indicated. © 2012 Movement Disorder Society.
Maria Stamelou, Araceli Alonso-Canovas, Kailash P Bhatia (2012)  Dystonia in corticobasal degeneration: a review of the literature on 404 pathologically proven cases.   Mov Disord 27: 6. 696-702 May  
Abstract: Dystonia is considered one of the classical features of corticobasal degeneration and is reported in up to 83% in clinical, not pathologically confirmed, series. Here, we aimed to establish the frequency and the clinical characteristics of dystonia in CBD by reviewing the literature on 404 pathologically proven cases. Further, we aimed to identify the frequency and characteristics of dystonia in all described phenotypes with CBD pathology. Dystonia was present in only 37.5% of the 296 cases with adequate information. The majority of the cases with dystonia presented with a corticobasal syndrome, and dystonia occurred in the first 2 years from disease onset, affecting the upper limb. In cases with dystonia that presented with a "dementia" phenotype, dystonia tended to appear later in the disease course and to more affect the cervical region and the face. With regard to the distribution of the phenotypes, fifty-four percent of 374 cases presented as corticobasal syndrome, 15% as frontotemporal dementia, and 10.7% as progressive supranuclear palsy. Dystonia and myoclonus were present in about half of all cases with corticobasal syndrome, implying that these features may not be as frequent in corticobasal syndrome as are akinetic-rigid syndrome and apraxia (100% and 86.3%, respectively). Dystonia and myoclonus almost co-occurred in our analysis, suggesting a possible association. In conclusion, despite dystonia being an inclusion criterion in all sets of clinical criteria for corticobasal degeneration, this was present in only one third of the pathologically proven cases presented here. More accurate characterization of dystonia in corticobasal degeneration would be of importance for clinical diagnosis and development of treatment strategies.
Maria Stamelou, Karin Tuschl, W K Chong, Andrew K Burroughs, Philippa B Mills, Kailash P Bhatia, Peter T Clayton (2012)  Dystonia with brain manganese accumulation resulting from SLC30A10 mutations: A new treatable disorder.   Mov Disord Aug  
Abstract: BACKGROUND: The first gene causing early-onset generalized dystonia with brain manganese accumulation has recently been identified. Mutations in the SLC30A10 gene, encoding a manganese transporter, cause a syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia. METHODS: We present 10-year longitudinal clinical features, MRI data, and treatment response to chelation therapy of the originally described patient with a proven homozygous mutation in SLC30A10. RESULTS: The patient presented with early-onset generalized dystonia and mild hyperbilirubinemia accompanied by elevated whole-blood manganese levels. T1-sequences in MRI showed hyperintensities in the basal ganglia and cerebellum, characteristic of manganese deposition. Treatment with intravenous disodium calcium edetate led to clinical improvement and reduction of hyperintensities in brain imaging. CONCLUSIONS: We wish to highlight this rare disorder, which, together with Wilson's disease, is the only potentially treatable inherited metal storage disorder to date, that otherwise can be fatal as a result of complications of cirrhosis. © 2012 Movement Disorder Society.
Maria Stamelou, Niccolo E Mencacci, Carla Cordivari, Amit Batla, Nick W Wood, Henry Houlden, John Hardy, Kailash P Bhatia (2012)  Myoclonus-dystonia syndrome due to tyrosine hydroxylase deficiency.   Neurology 79: 5. 435-441 Jul  
Abstract: To present a new family with tyrosine hydroxylase deficiency (THD) that presented with a new phenotype of predominant, levodopa-responsive myoclonus with dystonia due to compound heterozygosity of one previously reported mutation in the promoter region and a novel nonsynonymous mutation in the other allele, thus expanding the clinical and genetic spectrum of this disorder.
Yaroslav Winter, Annika E Spottke, Maria Stamelou, Nicole Cabanel, Karla Eggert, Günter U Höglinger, Friederike Sixel-Doering, Birgit Herting, Thomas Klockgether, Heinz Reichmann, Wolfgang H Oertel, Richard Dodel (2011)  Health-related quality of life in multiple system atrophy and progressive supranuclear palsy.   Neurodegener Dis 8: 6. 438-446 05  
Abstract: Objective: Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), known as atypical parkinsonian syndromes (APS), are neurodegenerative disorders with severe disability and decreased life expectancy. Little is known about the health-related quality of life (HrQoL) and its determinants in patients with those disorders. The objective of our cross-sectional study was to evaluate the HrQoL in patients with APS and to identify the determinants of HrQoL. Methods: A total of 101 consecutive patients with MSA (n = 54) and PSP (n = 47) were recruited in four German neurological centers. Disease severity was assessed using the Hoehn and Yahr stages and the Unified MSA Rating Scale. The HrQoL was evaluated using the EuroQol instrument (EQ-5D and EQ-VAS). Independent determinants of HrQoL were identified in multiple regression analyses. Results: The mean EQ-VAS score was 52% lower than that reported for the general population (36.9 ± 18.3 vs. 77.4 ± 19.0). Of the study participants, 63% reported severe problems in at least one dimension of the EQ-5D. Cerebellar dysfunction was associated with a more considerable reduction of HrQoL. Independent determinants of reduced HrQoL were female gender, <12 years of education, disease severity, a decreased number of persons in the household and depression. Conclusions: The HrQoL in MSA and PSP is considerably reduced. While therapeutic options in the treatment of motor symptoms remain restricted, greater attention should be paid to the treatment of depression, which was identified among independent determinants of HrQoL. Independent determinants of HrQoL should be considered when developing healthcare programs aimed at improving the HrQoL in APS.
Maria Stamelou, Mark J Edwards, Mark Hallett, Kailash P Bhatia (2011)  The non-motor syndrome of primary dystonia: clinical and pathophysiological implications.   Brain Sep  
Abstract: Dystonia is typically considered a movement disorder characterized by motor manifestations, primarily involuntary muscle contractions causing twisting movements and abnormal postures. However, growing evidence indicates an important non-motor component to primary dystonia, including abnormalities in sensory and perceptual functions, as well as neuropsychiatric, cognitive and sleep domains. Here, we review this evidence and discuss its clinical and pathophysiological implications.
Daniela Berg, Jana Godau, Claudia Trenkwalder, Karla Eggert, Iiona Csoti, Alexander Storch, Heiko Huber, Monica Morelli-Canelo, Maria Stamelou, Vincent Ries, Martin Wolz, Christine Schneider, Thérèse Di Paolo, Fabrizio Gasparini, Sam Hariry, Marc Vandemeulebroecke, Walid Abi-Saab, Katy Cooke, Donald Johns, Baltazar Gomez-Mancilla (2011)  AFQ056 treatment of levodopa-induced dyskinesias: Results of 2 randomized controlled trials.   Mov Disord 26: 7. 1243-1250 Jun  
Abstract: Study objectives were to assess the efficacy, safety, and tolerability of AFQ056 in Parkinson's disease patients with levodopa-induced dyskinesia. Two randomized, double-blind, placebo-controlled, parallel-group, in-patient studies for Parkinson's disease patients with moderate to severe levodopa-induced dyskinesia (study 1) and severe levodopa-induced dyskinesia (study 2) on stable dopaminergic therapy were performed. Patients received 25-150 mg AFQ056 or placebo twice daily for 16 days (both studies). Study 2 included a 4-day down-titration. Primary outcomes were the Lang-Fahn Activities of Daily Living Dyskinesia Scale (study 1), the modified Abnormal Involuntary Movement Scale (study 2), and the Unified Parkinson's Disease Rating Scale-part III (both studies). Secondary outcomes included the Unified Parkinson's Disease Rating Scale-part IV items 32-33. The primary analysis was change from baseline to day 16 on all outcomes. Treatment differences were assessed. Fifteen patients were randomized to AFQ056 and 16 to placebo in study 1; 14 patients were randomized to each group in study 2. AFQ056-treated patients showed significant improvements in dyskinesias on day 16 versus placebo (eg, Lang-Fahn Activities of Daily Living Dyskinesia Scale, P = .021 [study 1]; modified Abnormal Involuntary Movement Scale, P = .032 [study 2]). No significant changes were seen from baseline on day 16 on the Unified Parkinson's Disease Rating Scale-part III in either study. Adverse events were reported in both studies, including dizziness. Serious adverse events (most commonly worsening of dyskinesias, apparently associated with stopping treatment) were reported by 4 AFQ056-treated patients in study 1, and 3 patients (2 AFQ056-treated patient and 1 in the placebo group) in study 2. AFQ056 showed a clinically relevant and significant antidyskinetic effect without changing the antiparkinsonian effects of dopaminergic therapy. © 2011 Movement Disorder Society.
Maria Stamelou, Helena Christ, Alexander Reuss, Wolfgang Oertel, Günter Höglinger (2011)  Hypodipsia discriminates progressive supranuclear palsy from other parkinsonian syndromes.   Mov Disord 26: 5. 901-905 Apr  
Abstract: The objective of this study was to evaluate whether the sensation of thirst differs between patients with progressive supranuclear palsy (PSP), multiple system atrophy with predominant parkinsonism (MSA-P), and Parkinson's disease (PD).
Yaroslav Winter, Maria Stamelou, Nicole Cabanel, Friedericke Sixel-Döring, Karla Eggert, Günter U Höglinger, Birgit Herting, Thomas Klockgether, Heinz Reichmann, Wolfgang H Oertel, Richard Dodel, Annika E Spottke (2011)  Cost-of-illness in multiple system atrophy and progressive supranuclear palsy.   J Neurol Apr  
Abstract: Multiple system atrophy and progressive supranuclear palsy are disabling neurodegenerative disorders, also known as atypical parkinsonian syndromes. Currently, no health economic evaluations of these diseases are available. The objective of this study was to evaluate disease-related costs in German patients with multiple system atrophy and progressive supranuclear palsy and to identify cost-driving factors. We recruited 101 consecutive patients with multiple system atrophy (n = 54) and progressive supranuclear palsy (n = 47) in four German specialised movement disorder clinics. The health economic data were collected using comprehensive health economic questionnaires ("bottom-up" approach). Costs were calculated from the societal perspective in 2010 Euros. Independent cost-driving factors were identified in multiple regression analysis. The total semi-annual costs of atypical parkinsonian syndromes were EUR 16,670 (95% CI: 13,470-21,850). Direct costs accounted for 73% (inpatient care 31%, special equipment 24%, copayments of patients 21%, others 24%) and indirect costs for 27% of total costs. The economic burden imposed on patients by atypical parkinsonian syndromes accounted for 36% of their income. Independent cost-driving factors were younger age, disease severity, living without a partner and depression. The disease-related costs of atypical parkinsonian syndromes in Germany are high and above the costs reported for idiopathic Parkinson's disease. Disease-specific patterns of cost distributions in atypical parkinsonian syndromes and independent cost-drivers should be considered in future health economic evaluations and healthcare programs. The early diagnosis and treatment of depression in patients with atypical parkinsonian syndromes as well as programs aimed to improve social support will reduce disease-related costs.
Marcus M Unger, Jens C Möller, Katharina Mankel, Katrin Schmittinger, Karla M Eggert, Maria Stamelou, Karin Stiasny-Kolster, Katharina Bohne, Maren Bodden, Geert Mayer, Wolfgang H Oertel, Johannes J Tebbe (2011)  Patients with idiopathic rapid-eye-movement sleep behavior disorder show normal gastric motility assessed by the 13C-octanoate breath test.   Mov Disord 26: 14. 2559-2563 Dec  
Abstract: Delayed gastric emptying is a non-motor symptom of Parkinson's disease. Few data exist on gastric emptying in early-stage Parkinson's disease. In idiopathic rapid-eye-movement sleep behavior disorder, a presumable pre-motor stage of Parkinson's disease, gastric emptying has not yet been investigated.
M Stamelou, S Knake, W H Oertel, G U Höglinger (2011)  Magnetic resonance imaging in progressive supranuclear palsy.   J Neurol 258: 4. 549-558 Apr  
Abstract: Progressive supranuclear palsy (PSP) is a tauopathy, presenting clinically most often with a symmetrical akinetic-rigid syndrome, postural instability, supranuclear gaze palsy and frontal dementia. In the absence of reliably validated biomarkers, the diagnosis of PSP in vivo is presently based on clinical criteria, which to date do not include supporting imaging findings, as is accepted for other neurodegenerative diseases. However, data from conventional magnetic resonance imaging (MRI) and various advanced MRI techniques including magnetic resonance volumetry, voxel-based morphometry, diffusion-weighted and diffusion-tensor imaging, magnetization transfer imaging and proton resonance spectroscopy suggest that MRI can contribute valuable information for the differential diagnosis of PSP. We review here the presently published literature concerning MRI in PSP and discuss the potential role of MRI in differentiating PSP from other parkinsonian syndromes.
Günter U Höglinger, Nadine M Melhem, Dennis W Dickson, Patrick M A Sleiman, Li-San Wang, Lambertus Klei, Rosa Rademakers, Rohan de Silva, Irene Litvan, David E Riley, John C van Swieten, Peter Heutink, Zbigniew K Wszolek, Ryan J Uitti, Jana Vandrovcova, Howard I Hurtig, Rachel G Gross, Walter Maetzler, Stefano Goldwurm, Eduardo Tolosa, Barbara Borroni, Pau Pastor, Roger L Albin, Elena Alonso, Angelo Antonini, Manuela Apfelbacher, Steven E Arnold, Jesus Avila, Thomas G Beach, Sherry Beecher, Daniela Berg, Thomas D Bird, Nenad Bogdanovic, Agnita J W Boon, Yvette Bordelon, Alexis Brice, Herbert Budka, Margherita Canesi, Wang Zheng Chiu, Roberto Cilia, Carlo Colosimo, Peter P De Deyn, Justo García de Yebenes, Laura Donker Kaat, Ranjan Duara, Alexandra Durr, Sebastiaan Engelborghs, Giovanni Fabbrini, Nicole A Finch, Robyn Flook, Matthew P Frosch, Carles Gaig, Douglas R Galasko, Thomas Gasser, Marla Gearing, Evan T Geller, Bernardino Ghetti, Neill R Graff-Radford, Murray Grossman, Deborah A Hall, Lili-Naz Hazrati, Matthias Höllerhage, Joseph Jankovic, Jorge L Juncos, Anna Karydas, Hans A Kretzschmar, Isabelle Leber, Virginia M Lee, Andrew P Lieberman, Kelly E Lyons, Claudio Mariani, Eliezer Masliah, Luke A Massey, Catriona A McLean, Nicoletta Meucci, Bruce L Miller, Brit Mollenhauer, Jens C Möller, Huw R Morris, Chris Morris, Sean S O'Sullivan, Wolfgang H Oertel, Donatella Ottaviani, Alessandro Padovani, Rajesh Pahwa, Gianni Pezzoli, Stuart Pickering-Brown, Werner Poewe, Alberto Rabano, Alex Rajput, Stephen G Reich, Gesine Respondek, Sigrun Roeber, Jonathan D Rohrer, Owen A Ross, Martin N Rossor, Giorgio Sacilotto, William W Seeley, Klaus Seppi, Laura Silveira-Moriyama, Salvatore Spina, Karin Srulijes, Peter St George-Hyslop, Maria Stamelou, David G Standaert, Silvana Tesei, Wallace W Tourtellotte, Claudia Trenkwalder, Claire Troakes, John Q Trojanowski, Juan C Troncoso, Vivianna M Van Deerlin, Jean Paul G Vonsattel, Gregor K Wenning, Charles L White, Pia Winter, Chris Zarow, Anna L Zecchinelli, Laura B Cantwell, Mi Ryung Han, Allissa Dillman, Marcel P van der Brug, J Raphael Gibbs, Mark R Cookson, Dena G Hernandez, Andrew B Singleton, Matthew J Farrer, Chang-En Yu, Lawrence I Golbe, Tamas Revesz, John Hardy, Andrew J Lees, Bernie Devlin, Hakon Hakonarson, Ulrich Müller, Gerard D Schellenberg (2011)  Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy.   Nat Genet 43: 7. 699-705 06  
Abstract: Progressive supranuclear palsy (PSP) is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP (cases) and 3,247 controls (stage 1) followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the stage 1 SNPs that yielded P ⤠10(-3). We found significant previously unidentified signals (P < 5 à 10(-8)) associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component.
Susanne Knake, Marcus Belke, Katja Menzler, Ulrich Pilatus, Karla M Eggert, Wolfgang H Oertel, Maria Stamelou, Günter U Höglinger (2010)  In vivo demonstration of microstructural brain pathology in progressive supranuclear palsy: a DTI study using TBSS.   Mov Disord 25: 9. 1232-1238 Jul  
Abstract: We investigated DTI changes, potentially indicating alterations of microstructure and brain tissue integrity in 13 patients with probable progressive supranuclear palsy (PSP, Richardson syndrome) at stage III or less and 10 age-matched controls using a whole brain analysis of diffusion tensor imaging (DTI) data. DTI images were analyzed using tract-based spatial statistics, a hypothesis-free technique. Fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) were determined. In patients with PSP, significant increases in FA (P < 0.0001), an unspecific measure of microstructural tissue integrity, were found in the cerebellum and in the superior cerebellar peduncle bilaterally, in the fornix, the body of the corpus callosum and the olfactory region, when compared with age-matched healthy controls. Further, regional reductions in AD (P < 0.0001), an indicator of altered axonal integrity, were observed in the pons, the right substantia nigra and the cerebellar white matter bilaterally. Significant increases in RD (P < 0.0001), a potential measure of altered myelin integrity, occurred bilaterally in the superior cerebellar peduncle, the cerebellar white matter, the vermis of the cerebellum, the fornix, the body of the corpus callosum, and the olfactory region. RD values in the superior cerebellar peduncle discriminated patients with PSP and controls with high sensitivity (0.92) and specificity (1.0). The findings are supported by neuropathological studies. Our data suggest the usefulness of this clinically available new technique as a possible tool for differential diagnosis.
Oscar Arias-Carrión, Maria Stamelou, Eric Murillo-Rodríguez, Manuel Menéndez-González, Ernst Pöppel (2010)  Dopaminergic reward system: a short integrative review.   Int Arch Med 3: 10  
Abstract: ABSTRACT: Memory is an essential element to adaptive behavior since it allows consolidation of past experience guiding the subject to consider them in future experiences. Among the endogenous molecules that participate in the consolidation of memory, including the drug-seeking reward, considered as a form of learning, is dopamine. This neurotransmitter modulates the activity of specific brain nucleus such as nuclei accumbens, putamen, ventral tegmental area (VTA), among others and synchronizes the activity of these nuclei to establish the neurobiological mechanism to set the hedonic element of learning. We review the experimental evidence that highlights the activity of different brain nuclei modulating the mechanisms whereby dopamine biases memory towards events that are of motivational significance.
Maria Stamelou, Rohan de Silva, Oscar Arias-Carrión, Evangelia Boura, Matthias Höllerhage, Wolfgang H Oertel, Ulrich Müller, Günter U Höglinger (2010)  Rational therapeutic approaches to progressive supranuclear palsy.   Brain 133: Pt 6. 1578-1590 Jun  
Abstract: Progressive supranuclear palsy is a sporadic and progressive neurodegenerative disease, most often presenting as a symmetric, akinetic-rigid syndrome with postural instability, vertical supranuclear gaze palsy and frontal lobe deficits. It belongs to the family of tauopathies and involves both cortical and subcortical structures. Although the exact pathophysiology is not yet fully understood, several lines of evidence point to a crucial contribution from both genetic predisposition and mitochondrial dysfunction. Recently gained insights into the pathophysiology of this disease have led to several hypothesis-driven therapeutic approaches aiming at disease-modification rather than mere symptomatic neurotransmitter-replacement therapy. Agents targeting mitochondrial dysfunction have already shown a positive effect in a phase II study and further studies to verify and expand these results are ongoing. Clinical studies with agents targeting tau dysfunction such as tau-kinase inhibitors, tau-aggregation inhibitors and microtubule stabilizers are in preparation or ongoing. This review presents the current pathophysiological concepts driving these exciting therapeutic developments.
E Hattingen, H Lanfermann, S Menon, T Neumann-Haefelin, R DuMesnil de Rochement, M Stamelou, G U Höglinger, J Magerkurth, U Pilatus (2009)  Combined 1H and 31P MR spectroscopic imaging: impaired energy metabolism in severe carotid stenosis and changes upon treatment.   MAGMA 22: 1. 43-52 Feb  
Abstract: To evaluate if combined (1)H and (31)P MR spectroscopic imaging (MRSI) before and after treatment of severe internal carotid artery (ICA) stenosis detects significant changes in energy metabolism in the basal ganglia of both hemispheres.
Maria Stamelou, Andreas Matusch, David Elmenhorst, René Hurlemann, Karla M Eggert, Karl Zilles, Wolfgang H Oertel, Günter U Höglinger, Andreas Bauer (2009)  Nigrostriatal upregulation of 5-HT2A receptors correlates with motor dysfunction in progressive supranuclear palsy.   Mov Disord 24: 8. 1170-1175 Jun  
Abstract: A dysfunction of multiple neurotransmitter systems is assumed as a neurochemical basis of the akinetic-rigid syndrome of progressive supranuclear palsy (PSP). In vitro studies have produced conflicting results on the serotoninergic system in PSP. We, therefore, studied the binding potential of the serotonin 2A (5-HT(2A)) receptor ligand [18F]altanserin in 8 patients with clinically probable PSP and 13 healthy controls using positron emission tomography. We found an up-regulation of 5-HT(2A) receptors in the substantia nigra and, to a lower degree, in the striatum, while neocortical 5- HT(2A) receptor densities showed no changes upon partial-volume correction. Nigral and striatal receptor changes were significantly correlated with patients' scores of motor dysfunction (UPDRS III, PSP-rating scale) pointing to a functional relevance of the described findings.
Maria Stamelou, Ulrich Pilatus, Alexander Reuss, Jörg Magerkurth, Karla M Eggert, Susanne Knake, Merle Ruberg, Carmen Schade-Brittinger, Wolfgang H Oertel, Günter U Höglinger (2009)  In vivo evidence for cerebral depletion in high-energy phosphates in progressive supranuclear palsy.   J Cereb Blood Flow Metab 29: 4. 861-870 Apr  
Abstract: Indirect evidence from laboratory studies suggests that mitochondrial energy metabolism is impaired in progressive supranuclear palsy (PSP), but brain energy metabolism has not yet been studied directly in vivo in a comprehensive manner in patients. We have used combined phosphorus and proton magnetic resonance spectroscopy to measure adenosine-triphosphate (ATP), adenosine-diphosphate (ADP), phosphorylated creatine, unphosphorylated creatine, inorganic phosphate and lactate in the basal ganglia and the frontal and occipital lobes of clinically probable patients (N=21; PSP stages II to III) and healthy controls (N=9). In the basal ganglia, which are severely affected creatine in PSP patients, the concentrations of high-energy phosphates (=ATP+phosphorylated creatine) and inorganic phosphate, but not low-energy phosphates (=ADP+unphosphorylated creatine), were decreased. The decrease probably does not reflect neuronal death, as the neuronal marker N-acetylaspartate was not yet significantly reduced in the early-stage patients examined. The frontal lobe, also prone to neurodegeneration in PSP, showed similar alterations, whereas the occipital lobe, typically unaffected, showed less pronounced alterations. The levels of lactate, a product of anaerobic glycolysis, were elevated in 35% of the patients. The observed changes in the levels of cerebral energy metabolites in PSP are consistent with a functionally relevant impairment of oxidative phosphorylation.
A Strzelczyk, J C Möller, M Stamelou, A Matusch, W H Oertel (2008)  [Atypical Parkinson syndromes].   Nervenarzt 79: 10. 1203-20; quiz 1221-2 Oct  
Abstract: At the moment atypical Parkinson syndromes have unfavorable prognoses and show little response to dopaminergic medication. Early differential diagnosis of these disorders from idiopathic Parkinson syndrome is of pivotal clinical relevance. In case of future causal, neuroprotective therapeutic strategies, early diagnosis will allow a timely start of therapy. In the early stage of disease, it might be difficult clinically to distinguish multiple system atrophy, progressive supranuclear palsy, and corticobasal ganglionic degeneration from idiopathic Parkinson syndrome. Additional electrophysiological, imaging, and nuclear medical investigations may support the clinical diagnosis. During disease progression clinical signs indicative of an atypical Parkinson syndrome should always warrant reevaluation of the diagnosis.
Karla Eggert, Christoph Schrader, Michaela Hahn, Maria Stamelou, Anne Rüssmann, Reinhard Dengler, Wolfgang Oertel, Per Odin (2008)  Continuous jejunal levodopa infusion in patients with advanced parkinson disease: practical aspects and outcome of motor and non-motor complications.   Clin Neuropharmacol 31: 3. 151-166 May/Jun  
Abstract: We report here on the experience with continuous jejunal levodopa infusion in 13 German parkinsonian patients who have motor and nonmotor complications despite individually optimized oral treatment. The tolerability, efficacy, and the need for dose adjustment of levodopa infusion were followed-up prospectively. Thereby, we describe clinically relevant details for how to successfully initiate and handle this new treatment strategy.
Maria Stamelou, Alexander Reuss, Ulrich Pilatus, Jörg Magerkurth, Petra Niklowitz, Karla M Eggert, Andrea Krisp, Thomas Menke, Carmen Schade-Brittinger, Wolfgang H Oertel, Günter U Höglinger (2008)  Short-term effects of coenzyme Q10 in progressive supranuclear palsy: a randomized, placebo-controlled trial.   Mov Disord 23: 7. 942-949 May  
Abstract: Mitochondrial complex I appears to be dysfunctional in progressive supranuclear palsy (PSP). Coenzyme Q(10) (CoQ(10)) is a physiological cofactor of complex I. Therefore, we evaluated the short-term effects of CoQ(10) in PSP. We performed a double-blind, randomized, placebo-controlled, phase II trial, including 21 clinically probable PSP patients (stage < or = III) to receive a liquid nanodispersion of CoQ(10) (5 mg/kg/day) or matching placebo. Over a 6-week period, we determined the change in CoQ(10) serum concentration, cerebral energy metabolites (by (31)P- and (1)H-magnetic resonance spectroscopy), motor and neuropsychological dysfunction (PSP rating scale, UPDRS III, Hoehn and Yahr stage, Frontal Assessment Battery, Mini Mental Status Examination, Montgomery Asberg Depression Scale). CoQ(10) was safe and well tolerated. In patients receiving CoQ(10) compared to placebo, the concentration of low-energy phosphates (adenosine-diphosphate, unphosphorylated creatine) decreased. Consequently, the ratio of high-energy phosphates to low-energy phosphates (adenosine-triphosphate to adenosine-diphosphate, phospho-creatine to unphosphorylated creatine) increased. These changes were significant in the occipital lobe and showed a consistent trend in the basal ganglia. Clinically, the PSP rating scale and the Frontal Assessment Battery improved slightly, but significantly, upon CoQ(10) treatment compared to placebo. Since CoQ(10) appears to improve cerebral energy metabolism in PSP, long-term treatment might have a disease-modifying, neuroprotective effect.
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