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1. The Potential Added Value of Novel Hearing Therapeutics: An Early Health Economic Model for Hearing Loss

Author

Carl May, Evie Landry, Maroeska M. Rovers, Mirre Scholte, Yvette M Horstink, Janneke P.C. Grutters, Anne G M Schilder, and Rishi Mandavia

Subjects
medicine.medical_specialty, Hearing loss, Hearing Loss, Sensorineural, MEDLINE, Nice, State Medicine, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, 0302 clinical medicine, Hearing, Value for money, Health care, Added value, medicine, Humans, 030223 otorhinolaryngology, Intensive care medicine, computer.programming_language, business.industry, Analytic model, Hearing Loss, Sudden, Sensory Systems, Models, Economic, Otorhinolaryngology, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Economic model, Neurology (clinical), medicine.symptom, business, computer, 030217 neurology & neurosurgery
Abstract

Objective To construct an early health economic model to assess the potential added value of novel hearing therapeutics, compared with the current standard of care. We use idiopathic sudden sensorineural hearing loss (ISSNHL) as a case example, because it is a lead indication for several emerging hearing therapeutics. Methods A decision analytic model was developed to assess the costs and effects of using novel hearing therapeutics for patients with ISSNHL. This was compared to the current standard of care. Input data were derived from literature searches and expert opinion. The study adopted a healthcare perspective of the UK National Health Service. Four analyses were conducted: 1) headroom, 2) scenario, 3) threshold, 4) sensitivity. Results The decision analytic model showed that novel therapeutics for ISSNHL have potential value both in terms of improved patient outcomes, as well as incremental net monetary benefit (iNMB). The base case analysis revealed an iNMB of £39,032 for novel therapeutics compared with the current standard of care. Results of the threshold and scenario analysis revealed that age of treatment and severity of ISSNHL are major determinants of iNMB for novel therapeutics. Conclusion This article describes the first health economic model for novel therapeutics for hearing loss; and shows that novel hearing therapeutics can be cost-effective under NICE's cost-effectiveness threshold, with considerable room for improvement in the current standard of care. Our model can be used to inform the development of cost-effective hearing therapeutics; and help decision makers decide which therapeutics represent value for money.

Published
2020

2. Hypokinesia and Rigidity as Clinical Manifestations of Mitochondrial Encephalomyopathy: Report of Three Cases

Author

P. M. M. van Erven, H.O.M. Thijssen, Wim Ruitenbeek, Fons J. M. Gabreëls, M. W. I. M. Horstink, and W. O. Renier

Subjects
Male, Mitochondrial encephalomyopathy, medicine.medical_specialty, Adolescent, Energy metabolism, Computed tomography, Synaptic Transmission, Child Development, Developmental Neuroscience, Hypokinesia, Pyruvic Acid, medicine, Humans, Leigh disease, Child, Pyruvates, Pyruvate Metabolism, Gynecology, medicine.diagnostic_test, Brain Diseases, Metabolic, business.industry, Brain, Neuromuscular Diseases, medicine.disease, Magnetic Resonance Imaging, Sindrome de, Mitochondria, Muscle, Surgery, Pediatrics, Perinatology and Child Health, Neurology (clinical), Atrophy, Leigh Disease, medicine.symptom, Tomography, X-Ray Computed, business, Capsula interna, Follow-Up Studies
Abstract

SUMMARY Three patients are reported with a neurological disorder in which hypokinesia and rigidity were the most prominent clinical signs. On CT scan and MRI, two were found to have bilateral lesions in the striatum, mainly in the putamen, and the third had bilateral lesions in the posterior limb of the internal capsule. Laboratory investigations suggested abnormal pyruvate metabolism in all three cases, which was confirmed to skeletal muscle in two cases. In the third the cause was a NADH dehydrogenase defect. The sign and symptoms, the bilateral striatal lesions in two of the patients, and the abnormal pyruvate metabolism justify a classification of mitochondrial encephalomyopathy, resembling Leigh syndrome. This diagnosis must be considered for infants and children presenting with Parkinsonian signs, and mitochondrial energy metabolism should be investigated. RESUME Manifestations cliniques d'une encephalomyopathie mitochondriale a type d'hypokinesie et rigidite: trois cas L'article rapporte trois cas d'un trouble neurologique dans lequel l'hypokinesie et la rigidite constituaient les signes cliniques majeurs. Au scanner et IRM, deux malades presentaient des lesions bilaterales des corps stries, principalement du putamen; le troisieme presentait des lesions bilaterales de la branche posterieure de la capsule interne. Les investigations de laboratoire suggeraient un metabolisme pyruvique anormal dans les trois cas, confirme dans les muscles squelettiques dans deux cas. Dans le troisieme cas, l'origine de l'anomalie etait un defaut de NADH dehydrogenase. Les signes et symptomes, les lesions striees bilaterales dans deux cas, et le metabolisme pyruvique anormal, justifient de classer ces cas dans le cadre d'encephalomyopathie, ressemblant au syndrome de Leigh. Ce diagnostic doit ere envisage chez des nourrissons ou enfants presentant des signes parkinsoniens, et le metabolisme mitochondrial doit alors etre apprecie. ZUSAMMENFASSUNG Hypokinese und Rigiditat als klinische Manifestationen einer mitochondrischen Encephalomyopathie: Bericht uber drei Falle Es wird uber drei Patienten mit einer neurologischen Erkrankung berichtet, bei der die wichtigsten klinischen Symptome Hyperkinese und Rigiditat waren. Die CT und MRI Befunde zeigten bei zwei Patienten bilaterale Lasionen im Striatum, hauptsachlich im Putamen und beim dritten bilaterale Lasionen im hinteren Anteil der Capsula interna. Die Laborwerte lieβen in allen drei Fallen einen abnormen Pyruvatstoffwechsel vermuten, der bei zwei Patienten durch eine Skelettmuskeluntersuchung bestatigt werden konnte. Beim dritten fand sich ein NADH Dehydrogenasedefekt als Ursache. Die Befunde und Symptome, die bilateralen Lasionen im Striatum bei zwei Patienten und der abnorme Pyruvatstoffwechsel rechtfertigen eine Klassifikation der mitochondrischen Encephalomyopathie, ahnlich dem Leigh Syndrom. Diese Diagnose sollte bei Sauglingen und Kindern mit Parkinson ahnlichen Befunden berucksightigt werden und es sollte der Energiestoffwechsel der Mitochondrien untersucht werden. RESUMEN Hipocinesia y rigidez como manifestaciones clinicas de encefalomiopatia mitocondrial: aportacion de tres casos Se aportan tres pacientes con una alteracion neurologica en que la hipocinesia y la rigidez eran los signos clinicos mas prominentes. En el Scanner cerebral y el MRI se hallo que dos tenian lesiones bilaterales en el estriado, sobre todo en el putamen y el tercero tenia lesiones bilaterales en el brazo posterior de la capsula interna. Las investigaciones de laboratorio sugirieron un metabolismo anomalo del piruvato en los tres casos, que se confirmo en el musculo esqueletico en dos casos. En el tercero, la causa era un defecto de NADH deshidrogenasa. Los signos y sintomas, las lesiones estriadas en dos pacientes y el anormal metabolismo del piruvato justifican una clasificacion de encefalomiopatia mitocondrial parecida al sindrome de Leigh. Este diagnostico debe ser considerado en lactantes y ninos con signos de Parkinsonismo y debe investigarse el metabolismo energetico mitocondrial.

Published
2008
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3. Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123I]-FP-CIT SPECT imaging: The [123I]-FP-CIT study group

Author

Hani T.S. Benamer, Johannes D. Speelman, Wolfgang H. Oertel, Donald G. Grosset, M. H. I. M. Horstink, K. Joseph, S. Gacinovic, A. J. Lees, Jan Booij, K. De Bruin, J. Schwarz, Rudi Dierckx, Donald M. Hadley, Danny Decoo, M. Doder, H. J. W. A. Sips, Jim Patterson, C. Van Der Linden, Klaus Tatsch, Helmut Hoeffken, Durval C. Costa, V. Ries, J. Versijpt, Oliver Pogarell, and E. A. Van Royen

Subjects
Adult, Male, Essential Tremor, Neurological disorder, Diagnosis, Differential, Iodine Radioisotopes, 123I-FP-CIT, Reference Values, Spect imaging, Visual assessment, medicine, Humans, Dominance, Cerebral, Aged, Aged, 80 and over, Observer Variation, Tomography, Emission-Computed, Single-Photon, Essential tremor, business.industry, Putamen, Parkinsonism, Parkinson Disease, Middle Aged, medicine.disease, Corpus Striatum, Neurology, Female, Neurology (clinical), Differential diagnosis, Psychology, Nuclear medicine, business, Tropanes
Abstract

OBJECTIVE: To evaluate whether visual assessment of [I-123]-FP-CIT (DaTSCAN(TM), Nycomed Amersham, pie) single photon emission computerized tomography (SPECT) images can differentiate between parkinsonism and essential tremor (ET). METHODS: [I-123]-FP-CIT SPECT imaging was conducted in a six-center study of 158 patients with a clinical diagnosis of parkinsonism compared with 27 ET cases and 35 healthy volunteers. Striatal uptake of the radioligand was graded normal or abnormal, and abnormal images were further graded to three levels of severity. An institutional read whereby each center visually assessed the images blinded to the clinical data and a consensus blinded read by a panel of five was undertaken. RESULTS: The institutional reading scored 154 of 158 cases of parkinsonism abnormal, all 27 cases of ET as normal, and 34 of 35 healthy volunteers as normal compared with the consensus blinded read scoring 150 cases of parkinsonism as abnormal, 25 ET cases as normal, and 33 healthy volunteers as normal. Sensitivity for the clinical diagnosis of parkinsonism was 97% and specificity for ET was 100% for the institutional read, whereas sensitivity was 95% and specificity 93% for the consensus blinded read. Semiquantitative analysis of specific: nonspecific caudate and putamen uptake were consistent with the results of visual inspection. CONCLUSION: Visual assessment of [I-123]-FP-CIT SPECT images is an easily applied diagnostic test which is helpful in the differential diagnosis of tremor disorders and in confirming a clinical diagnosis of a hypokinetic-rigid syndrome.

Published
2000
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4. Functionally important correlated motions in the single-stranded DNA-binding protein encoded by filamentous phage Pf3

Author

Michael Nilges, Lennard M. Horstink, Roger Abseher, and Cornelis W. Hilbers

Subjects
Models, Molecular, Magnetic Resonance Spectroscopy, Protein Conformation, Dynamics (mechanics), Combined use, DNA, Single-Stranded, Cooperative binding, Biology, DNA-Binding Proteins, Viral Proteins, Crystallography, Molecular dynamics, chemistry.chemical_compound, Inovirus, chemistry, Structural Biology, DNA, Viral, Single-stranded DNA binding, Biophysics, Thermodynamics, Relaxation (physics), Dimerization, Molecular Biology, DNA
Abstract

To elucidate the interplay between different parts of dimeric single-stranded DNA-binding proteins we have studied the correlated motions in the protein encoded by filamentous phage Pf3 via the combined use of 15N-NMR relaxation experiments, molecular dynamics simulations and essential dynamics calculations. These studies provide insight into the mechanism underlying the protein-DNA binding reaction. The most important motions can be described by a few essential modes. Most outstanding is the correlated symmetric motion of the DNA-binding wings, which are far apart in the structure. This motion determines the access of DNA to the DNA-binding domain. A correlation between the motion of the DNA-binding wing and the complex loop is indicated to play a role in the cooperative binding of the protein to DNA. These motions are in the nanosecond regime in correspondence with the 15N-NMR relaxation experiments.

Published
1999
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5. Essential spaces defined by NMR structure ensembles and molecular dynamics simulation show significant overlap

Author

Cornelis W. Hilbers, Lennard M. Horstink, Michael Nilges, and Roger Abseher

Subjects
Quantitative Biology::Biomolecules, Chemistry, Component (thermodynamics), Protein dynamics, Covariance, Space (mathematics), Biochemistry, Molecular dynamics, Protein structure, Structural Biology, Computational chemistry, Principal component analysis, Statistical physics, Molecular Biology, Eigenvalues and eigenvectors
Abstract

Large concerted motions of proteins which span its "essential space," are an important component of protein dynamics. We investigate to what extent structure ensembles generated with standard structure calculation techniques such as simulated annealing can capture these motions by comparing them to long-time molecular dynamics (MD) trajectories. The motions are analyzed by principal component analysis and compared using inner products of eigenvectors of the respective covariance matrices. Two very different systems are studied, the beta-spectrin PH domain and the single-stranded DNA binding protein (ssDBP) from the filamentous phage Pf3. A comparison of the ensembles from NMR and MD shows significant overlap of the essential spaces, which in the case of ssDBP is extraordinarily high. The influence of variations in the specifications of distance restraints is investigated. We also study the influence of the selection criterion for the final structure ensemble on the definition of mobility. The results suggest a modified criterion that improves conformational sampling in terms of amplitudes of correlated motion.

Published
1998
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6. Reliance on external cues for movement initiation in Parkinson's disease: evidence from movement-related potentials

Author

M. W. I. M. Horstink, Peter Praamstra, Dick F. Stegeman, and Alexander R. Cools

Subjects
Male, Visual perception, Parkinson's disease, Movement, Farmacotherapie van psychomotorische ziektebeelden, fundamenteel en toegepast onderzoek, Sensory system, Contingent Negative Variation, Electroencephalography, Neurofysiologische analyse van bewegingsstoornissen ihb de ziekte van Parkinson, Degenerative disease, Reference Values, medicine, Reaction Time, Neurophysiological analysis of movement disorders with emphasis on Parkinson's disease, Humans, Evoked Potentials, Aged, medicine.diagnostic_test, Parkinson Disease, Neurophysiology, Middle Aged, medicine.disease, Pharmacotherapy of psychomotor diseases, fundamental and applied research, Contingent negative variation, medicine.anatomical_structure, Evoked Potentials, Visual, Female, Neurology (clinical), Cues, Psychology, Neuroscience, Photic Stimulation, Motor cortex
Abstract

The aim of this study was to investigate the neurophysiological mechanisms underlying Parkinson's disease patients' increased reliance on external cues for the initiation of movement. Lateralized movement-related cortical potentials were recorded in a noise-compatibility task with seven patients and seven age-matched control subjects. In this two-choice task, visual stimuli containing incompatible target and distractor elements, which simultaneously instructed for responses from both hands, initially caused activation of the motor cortex controlling the wrong response hand. The incorrect response activation was of higher amplitude in patients than in control subjects, causing a longer response delay relative to response times when target and distractors instructed the same hand. In addition, hand-specific motor cortex activation started earlier in patients than in control subjects. These results indicate that visual stimuli exerted an earlier and stronger influence on movement initiation in patients than in control subjects. We hypothesize that information from sensory stimuli relevant for the generation of a response can have rapid access to motor structures in Parkinson's disease patients, thereby facilitating the initiation of movement. The findings may reflect a compensatory mechanism, but could also be related to excitability changes in the motor cortex intrinsic to the pathophysiology of Parkinson's disease.

Published
1998

7. Dipole source analysis suggests selective modulation of the supplementary motor area contribution to the readiness potential

Author

M. W. I. M. Horstink, Peter Praamstra, Dick F. Stegeman, and Alexander R. Cools

Subjects
Adult, Male, Central Nervous System, algemeen [Geneeskunde], Logic, Models, Neurological, Farmacotherapie van psychomotorische ziektebeelden, fundamenteel en toegepast onderzoek, Contingent Negative Variation, Medical sciences, Central Nervous System Diseases, Medical, Modulation (music), an Event-Related Potentials Investigation [Movement preparation in Parkinson"s disease], medicine, Humans, Psychology, De planning van beweging bij de ziekte van Parkinson, een Event-Related Potentials onderzoek, Bescherming en bevordering van de menselijke gezondheid, Dominance, Cerebral, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Niet-toepassingsgericht onderzoek, Pharmacology, Behavior, Supplementary motor area, Movement (music), Animal, General Neuroscience, Motor Cortex, Neurosciences, Psychology, Medical, Geneeskunde: algemeen, Pharmacotherapy of psychomotor diseases, fundamental and applied research, SMA, Life sciences, Contingent negative variation, Electrophysiology, Functional imaging, Disease Models, Animal, medicine.anatomical_structure, Neurology, Disease Models, Medicine, Female, Neurology (clinical), Neuroscience, Biologie, Motor cortex
Abstract

The readiness potential preceding voluntary movement is modulated by the mode of movement selection, i.e. it has a higher amplitude preceding freely selected than before prescribed movements (Praamstra, P., Stegeman, D.F., Horstink, M.W.I.M., Brunia, C.H.M. and Cools, A.R. Movement-related potentials preceding voluntary movement are modulated by the mode of movement selection. Exp. Brain Res., 1995, 103: 429-439). One cortical area that is likely to be involved in this modulation is the supplementary motor area (SMA). Recent attempts to elucidate the neural generators of the readiness potential using spatiotemporal dipole source analysis, however, failed to establish a significant SMA contribution to the readiness potential. This might be explained by a failure of the proposed analyses to discriminate between SMA and motor cortex contributions to the readiness potential. We applied a dipole source analysis approach that better separates these overlapping source activities. The resulting source model includes an SMA source generating pre-movement activity consistent with evidence from intracranial recordings in humans. The SMA source accounts almost completely for the modulation of the readiness potential by different modes of movement selection. On the basis of these results, the relation between scalp-recorded movement-related activity, intracranially recorded potentials, and findings from functional imaging studies of voluntary movement, appears more transparent than suggested by previous dipole source analyses of premovement potentials.

Published
1996

8. Movement preparation in Parkinson's disease Time course and distribution of movement-related potentials in a movement precueing task

Author

M. W. I. M. Horstink, Alexander R. Cools, Dick F. Stegeman, Peter Praamstra, and Antje S. Meyer

Subjects
Adult, Male, medicine.medical_specialty, Parkinson's disease, Movement, Electromyography, Audiology, Lateralization of brain function, Central nervous system disease, Degenerative disease, Task Performance and Analysis, an Event-Related Potentials Investigation [Movement preparation in Parkinson"s disease], Reaction Time, Humans, Medicine, De planning van beweging bij de ziekte van Parkinson, een Event-Related Potentials onderzoek, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Aged, Lateralized readiness potential, medicine.diagnostic_test, business.industry, Parkinson Disease, Middle Aged, Neurophysiology, medicine.disease, Contingent negative variation, Evoked Potentials, Visual, Female, Neurology (clinical), business, Neuroscience
Abstract

Contains fulltext : 27996.pdf (Publisher’s version ) (Open Access) Investigations of the effects of advance information on movement preparation in Parkinson's disease using reaction time (RT) measures have yielded contradictory results. In order to obtain direct information regarding the time course of movement preparation, we combined RT measurements in a movement precueing task with multi-channel recordings of movement-related potentials in the present study. Movements of the index and middle fingers of the left and right hand were either precued or not by advance information regarding the side (left or right hand) of the required response. Reaction times were slower for patients than for control subjects. Both groups benefited equally from informative precues, indicating that patients utilized the advance information as effectively as control subjects. Lateralization of the movement-preceding cerebral activity [i.e. the lateralized readiness potential (LRP)] confirmed that patients used the available partial information to prepare their responses and started this process no later than controls. In conjunction with EMG onset times, the LRP onset measures allowed for a fractionation of the RTs, which provided clues to the stages where the slowness of Parkinson's disease patients might arise. No definite abnormalities of temporal parameters were found, but differences in the distribution of the lateralized movement-preceding activity between patients and controls suggested differences in the cortical organization of movement preparation. Differences in amplitude of the contingent negative variation (CNV) and differences in the way in which the CNV was modulated by the information given by the precue pointed in the same direction. A difference in amplitude of the P300 between patients and controls suggested that preprogramming a response required more effort from patients than from control subjects.

Published
1996
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9. Sequence Analysis by NMR Spectroscopy of the Peptide Lantibiotic Epilancin K7 from Staphylococcus epidermidis K7

Author

Angelika Frey, Ruud N.H. Konings, Lennard M. Horstink, Cornelis W. Hilbers, Mart Van De Kamp, Jörg W. Metzger, Henno W. van den Hooven, Frank J. M. Van De Ven, and Hans-Georg Sahl

Subjects
Alanine, Magnetic Resonance Spectroscopy, Molecular Structure, Edman degradation, Stereochemistry, Sequence analysis, Molecular Sequence Data, Protein primary structure, Nuclear magnetic resonance spectroscopy, Biochemistry, Anti-Bacterial Agents, chemistry.chemical_compound, Bacteriocins, chemistry, Staphylococcus epidermidis, Organic chemistry, Amino Acid Sequence, Peptides, Peptide sequence, Two-dimensional nuclear magnetic resonance spectroscopy, Lanthionine
Abstract

The amino acid sequence of the novel lantibiotic epilancin K7 from Staphylococcus epidermidis K7 was determined by NMR spectroscopy. NMR spectroscopy was used because sequencing by conventional Edman degradation techniques was prohibited by internal sequence blocks owing to the presence of modified residues. Epilancin K7 consists of 31 residues, including two alpha,beta-didehydroalanine (one-letter code U) and two alpha,beta-didehydrobutyrine (O) residues, one lanthionine (A-S-A), two beta-methyllanthionines (A*-S-A), and six lysines. Epilancin K7 has a molecular mass of 3032 +/- 1.5 Da. The amino acid sequence of epilancin K7 was derived from both through-space dipolar proton-proton interactions and through-bond scalar proton-carbon interactions as detected by two-dimensional 1H-NOESY, 1H-ROESY and three-dimensional 1H-TOCSY-NOESY, and by two-dimensional 1H,13C-heteronuclear multiple-bond correlation spectroscopy, respectively. The sequence is as follows: [sequence: see text] The N-terminal residue X partly resembles an alanine but its exact nature is unclear. The organization of the sulfide-bridge-containing (beta-methyl-)lanthionines was revealed by 1H-NMR and 1H,13C-NMR spectroscopy. Epilancin K7 has a linear structure and a high positive net charge, and therefore is classified as a type-A lantibiotic. NMR analysis of a degraded though still active form of epilancin K7 showed that two N-terminal residues of epilancin K7 were missing, owing to decomposition at the alpha,beta-didehydro alanine at position 3; it was called the epilancin K7-(3-31)-peptide (peptide fragment of epilancin K7 consisting of positions 3-31). The usefulness of three-dimensional 1H-TOCSY-NOESY, and two-dimensional 1H,13C-heteronuclear multiple-bond correlation spectroscopy at natural abundance for the study of (modified) polypeptides is demonstrated.

Published
1995
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10. Fourth meeting of the European Neurological Society 25–29 June 1994 Barcelona, Spain

Author

H. Hattig, C. Delli Pizzi, M. C. Addonizio, Michelle Davis, A. R. Giovagnoli, L. Florensa, M. Roth, J. de Kruijk, Francisco Lacruz, Ph. Dewailly, A. Toygar, C. Avendano, P.P. De Deyn, J. F. Hurtevent, F. Lomeila, T. W. Wong, Gordon T. Plant, M. Bud, H. J. Willison, DH Miller, D. W. Langdon, R. Cioni, J. Servan, A. Kaygisiz, E. Racadot, D. B. Schens, E. Picciola, L. Falip, C. Bouchard, J. Jotova, A. Jorge-Santamaria, P. Misra, A. Dufour, C. P. Panagopoulos, A. Venneri, B. Sredni, B. Angelard, M. Janelidze, M. Carreno, J. Obenberger, J. Pouget, H. W. Moser, R. Kaufmann, J. A. Molina, D. Linden, A. Martin Urda, E. Uvestad, A. Krone, J. P. Cochin, J. Mallecourt, A. Cambon-Thomsen, K. Violleau, P. Osschmann, A. M. Durocher, E. Bussaglia, D. M. Danielle, H. Efendi, C. Van Broeckhoven, K. G. Jordan, W. Rautenberg, C. Iniguez, J. M. Delgado, Graham Watson, M. Lawden, Gareth J. Barker, K. Stiasny, James T. Becker, G. Campanella, E. Peghi, A. Poli, A. Haddad, T. Yamawaki, Giacomo P. Comi, S. Sotgiu, B. Ersmark, A. Pomes, M. Ziegler, P. Ferrante, P. Ruppi, H. KuÇukoglu, R. Bouton, U. K. Rinne, P. Vieregge, M. Dary, P. Giunti, Peter J. Goadsby, S. Jung, E. Secor, A. Steinberg, N. Vila, M. A. Hernandez, M. Cursi, A. Enqelhardt, A. Engelhardt, J. Veitch, F. Di Silverio, F. Arnaud, B. Neundörfer, R. Brucher, Dominique Caparros-Lefebvre, B. Meyer, Marianne Dieterich, M. H. Snidaro, R. Gomez, R. Cerbo, M. Ragno, J. M. Vance, S. Nemni, A. Caliskan, F. Barros, I. Velcheva, D. Ceballos-Baumann, V. Barak, A. Avila, N. Antonova, F. Resche, S. Pappata, L. Varela, S. R. Silveira Santos, A. Cammarota, L. Naccache, Y. Nara, E. Tournier-Lasserves, R. Mobner, T. Chase, A. Ensenyat, J. Ulrich, G. Giegerich, M. Rother, M. Revilla, N. Nitschke, K. Honczarenko, E. Basart Tarrats, J. Blin, B. Jacob, J. Santamaria, S. Knezevic, J. L. Castillo, M. Antem, J. Colomer, O. Busse, Didier Hannequin, S. Carrier, J. B. Ruidavets, C. Rozman, J. Bogoussslavsky, J. Pascual Calvet, E. Monros, J. M. Polo, M. Zucconl, Javier Muruzabal, R. R. Allen, R. Rivolta, K. Haugaard, A. Nespolo, K. Hoang-Xuang, G. Bussone, T. Avramidis, E. Corsini, Christiana Franke, T. Vinogradova, H. Boot, K. Vestergaard, G. H. Jansen, N. Argentino, M. Raltzig, W. Linssen, Mark B. Pepys, P. Roblot, L. Lauritzen, E. Fainardi, D. Morin, T. X. Arbizu Urdiain, J. Wollenhaupt, S. Bostantjopoulou, G. Pavesi, A. D. Forman, Giovanni Fabbrini, D. Jean, J. J. Archelos, M. I. Blanchs, M. Del Gobbo, Anna Carla Turconi, Ch. Derouesné, Elio Scarpini, A. Visbeck, P. Castejon, J. P. Renou, F. Mounier-Vehier, G. Potagas, Ch. Duyckaerts, A. Filla, R. Schneider, G. Ronen, K. Nagata, J. P. Vedel, A. Henneberg, G. van Melle, C. Baratti, H. Knott, M. C. Prevett, A. Bes, B. Metin, Jos V. Reempts, L. Martorell, Mefkure Eraksoy, H. O. Handwerker, D. S. Younger, O. Oktem, D. Frongillo, C. Soriano-Soriano, L. Niehaus, F. Zipp, A. Tartaro, S Newman, R. H. Browne, P. Davous, R. Sanchez, M. Muros, M. E. Kornhuber, A. Lavarone, M. Mohr, M. R. Garcia, S. Russell, H. Kellar-Wood, M. R. Tola, B. Ostermeyer, Ch. Tzekov, K. Sartor, E. B. Ringelstein, P. P. Gazzaniga, Paul Krack, H. Fidaner, H. Rico, T. Dbaiss, F. Alameda, E. Torchiana, L. Rumbach, I. Charques, J. M. Bogaard, C. D. Frith, L. J. Rappelle, R. Brenner, A. Joutel, K. Fuxe, G. HÄcker, M. J. Blaser, J. Valls-SolÇ, G. Ulm, M. Alberdi, A. Bock, F. W. Bertelsmann, U. Wieshmann, J. Visa, J. R. Lupski, D. D'Amico, L. M. P. Ramos, A. A. Vanderbark, R. Horn, M. Warmuth, Dietmar Kühne, Mark S. Palmer, C. Ehrenheim, E. Canga, S. Viola, O. Scarpino, P. Naldi, R. Almeida, A. A. Raymond, J. Gamez, Stephan Arnold, A. DiGiovanni, J. Dalmau, C. C. Chari, H. F. Beer, J. C. Koetsier, J. Iriarte, E. Yunis, J. Casadevall, E. Le Guern, E. Stenager, S. R. Benbadis, J. M. Warter, F. Burklin, I. Theodorou, L. Johannesen, G. A. Graveland, X. Leclerc, I. Vecchio, L. Ozelius, G. Nicoletti, R. K. Gherardi, E. Esperet, M. L. Delodovici, F. Cattin, F. Paiau, Giorgio Sacilotto, C. A. J. Broere, D. Chavdarov, J. P. Willmer, C. H. Hawkes, Th. Naegele, E. Ellie, E. Dartigues, M. J. Guardiola, S. Hesse, Z. Levic, Marco Rovaris, P. Saugeir-Veber, B. A. Yaqub, H. F. Durwen, R. Larumbe, J. Ballabrina, M. Sendtner, J. Röther, M. Horstink, C. Kluglein, M.P. Montesi, H. Apaydin, J. Montoya, E. Waubant, Ch. Verellen-Dunoulin, A. Nicolai, J. Lopez-Delval, R. Lemon, G. Cantinho, E. Granieri, A. Zeviani, Wolfgang H. Oertel, U. Ficola, V. Di Piero, V. Fragola, K. Sabev, M. V. Guitera, I. Turki, F. Bolgert, P. Ingrand, J. M. Gobernado, L. M. E. Grimaldi, S. Baybas, B. Eymard, Y. Rolland, Y. Robitaille, Ta. Pampols, P. J. Koehler, A. Carroacedo, J. Vilchez, S. Di Vittorio, I. R. Rise, T. Nagy, M. Kuffner, E. Palazzini, A. Ott, J. Pruim, T. X. Arbizu, E. Manetti, C. Cervera, S. Felber, G. Gursoy, J. Scholz, G. A. Buscaino, M. S. Chen, A. Pascual, J. Hazan, J. U. Gajda, J. G. Cea, G. Bottini, G. Damalik, F. Le Doze, G. Bonaldi, J. M. Hew, C. Messina, A. M. Kennedy, J. M. Carney, N. M. F. 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Brasic, W. Heide, I. Santilli, W. M. Korn, D. Selcuki, M. J. Barrett, D. Krieger, T. Leon, T. Houallah, M. Tournilhac, C. Nos, D. Chavot, F. Barbieri, F. J. Jimenez-Jimenez, J. Muruzabal, K. Poeck, A. Sennlaub, L. M. Iriarte, L. G. Lazzarino, C. Sanz, P. A. Fischer, S. D. Shorvon, R. Hoermann, F. Delecluse, M. Krams, O. Corabianu, F. H. Hochberg, Christopher J. Mathias, B. Debachy, C. M. Poser, L. Delodovici, A. Jimenez-Escrig, F. Baruzzi, F. Godenberg, D. Cucinotta, P. J. Garcia Ruiz, K. Maier-Hauff, P. R. Bar, R. Mezt, R. Jochens, S. Karakaneva, C. Roberti, E. Caballero, Joseph E. Parisi, M. Zamboni, T. Lacasa, B. Baklan, J. C. Gautier, J. A. Martinez-Matos, W. Pollmann, G. Thomas, L. Verze, E. Chleide, R. Alvarez Sala, I. Noel, E. Albuisson, O. Kastrup, S. I. Rapoport, H. J. Braune, H. Lörler, M. Le Merrer, A. Biraben, S. Soler, S. J. Taagholt, U. Meyding-Lamadé, K. Bleasdale-Barr, Isabella Moroni, Y. Campos, J. Matias-Guiu, G. Edan, M. G. Bousser, John B. Clark, J. Garcia de Yebenes, N. K. Olsen, P. Hitzenberger, S. Einius, Aj Thompson, Ch. J. Vecht, T. Crepin-Leblond, Klaus L. Leenders, A. Di Muzio, L. Georgieva, René Spiegel, K. Sabey, D. Ménégalli, J. Meulstee, U. Liszka, P. Giral, C. Sunol, J. M. Espadaler, A. D. Crockar, K. Varli, G. Giraud, P. J. Hülser, A. Benazzouz, A. Reggio, M. Salvatore, K. Genc, M. Kushnir, S. Barbieri, J. Ph. Azulay, M. Gianelli, N. Bathien, A. AlMemar, F. Hentati, I. Ragueneau, F. Chiarotti, R. C. F. Smits, A. K. Asbury, F. Lacruz, B. Muller, Alan J. Thompson, Gordon Smith, K. Schmidt, C. Daems Monpeun, Juergen Weber, A. Arboix, G. R. Fink, A. M. Cobo, M. Ait Kaci Ahmed, E. Gencheva, Israel-Biet, G. Schlaug, P. De Jonghe, Philip Scheltens, K. Toyka, P. Gonzalez-Porque, A. Cila, J. M. Fernandez, P. Augustin, J. Siclia, S. Medaglini, D. E. Ziogas, A. Feve, L. Kater, G. J. E. Rinkel, D. Leppert, Rüdiger J. Seitz, S. Ried, C. Turc-Carel, G. Smeyers, F. Godinho, M. Czygan, M. Rijntjes, E. Aversa, M. Frigo, Leif Østergaard, J. L. Munoz Blanco, A. Cruz-Matinez, J. De Reuck, C. Theillet, T. Barroso, V. Oikonen, Florence Lebert, M. Kilinc, C. Cordon-Cardon, G. Stoll, E. Thiery, F. Pulcinelli, J. Solski, M. Schmiegelow, L. J. Polman, P. Fernandez-Calle, C. Wikkelso, M. Ben Hamida, M. Laska, E. Kott, W. Sulkowski, C. Lucas, N. M. Bornstein, D. Schmitz, M. W. Lammers, A. de Louw, R. J. S. Wise, P. A. van Darn, C. Antozzi, P. Villanueva, P. H. E. Hilkens, C. Constantin, W. Ricart, A. Wolf, M. Gamba, P. Maguire, Alessandro Padovani, B. M. Patten, Marie Sarazin, H. Ackermann, L. Durelli, S. Timsit, Sebastian Jander, B. W. Scheithauer, G. Demir, J. P. Neau, P. Barbanti, A. Brand, N. AraÇ, V. Fischer-Gagnepain, R. Marchioli, G. Serratrice, C. Maugard-Louboutin, G. T. Spencer, D. Lücke, G. Mainardi, K. Harmant Van Rijckevorsel, G. B. Creel, R. Manzanares, Francesco Fortunato, A. May, J. Workman, K. Johkura, E. Fernandez, Carlo Colosimo, L. Calliauw, L. Bet, Félix F. Cruz-Sánchez, M. Dhib, H. Meinardi, F. Carrara, J. Kuehnen, C. Peiro, H. Lassmann, K. Skovgaard Olsen, A. McDonald, L. Sciulli, A. Cobo, A. Monticelli, B. Conrad, J. Bagunya, J. Benitez, V. Desnizza, B. Dupont, O. Delrieu, D. Moraes, J. J. Heimans, F. Garcia Rio, M. Matsumto, A. Fernandez, R. Nermni, R. Chalmers, M. J. Marchau, F. Aguado, P. Velupillai, P. J. Martin, P. Tassan, V. Demarin, A. Engelien, T. Gerriets, Comar, J. L. Carrasco, J. P. Pruvo, A. Lopez de Munain, D. Pavitt, J. Alarcon, Chris H. Polman, B. Guldin, N. Yeni, Hartmut Brückmann, N. Wilczak, H. Szwed, R. Causaran, G. Kyriazis, M. E. Westarp, M. Gasparini, N. Pecora, J. M. Roda, E. Lang, V. Scaioli, David R. Fish, D. Caputo, O. Gratzl, R. Mercelis, A. Perretti, G. Steimetz, I. Link, C. Rigoletto, A. Catafau, G. Lucotte, M. Buti, G. Fagiolari, A. Piqueras, C. Godinot, J. C. Meurice, Erodriguez J. Dominigo, F. Lionnet, H. Grzelec, David J. Brooks, P. M. G. Munro, F. X. Weilbach, M. Maiwald, W. Split, B. Widjaja-Cramer, V. Ozturk, J. Colas, E. Brizioli, J. Calleja, L. Publio, M. Desi, R. Soffietti, P. Cortinovis-Tourniaire, E. F. Gonano, G. Cavaletti, S. Uselli, K. Westerlind, H. Betuel, C. O. Dhiver, H. Guggenheim, M. Hamon, R. Fazio, P. Lehikoinen, A. Esser, B. Sadzot, G. Fink, Angelo Antonini, D. Bendahan, V. Di Carlo, G. Galardi, A. F. Boller, M. Aksenova, Del Fiore, V. de la Sayette, H. Chabriat, A. Nicoletti, A. Dilouya, M. L. Harpin, E. Rouillet, J. Stam, A. Wolters, M. R. Delgado, Eduardo Tolosa, G. Said, A. J. Lees, L. Rinaldi, A. Schulze-Bonhage, MA Ron, C. Lefebvre, E. W. Radü, R. Alvarez, M. L. Bots, P. Reganati, S. Palazzi, A. Poggi, N. J. Scolding, V. Sazdovitch, T. Moreau, E. Maes, M. A. Estelies, P. Petkova, Jose-Felix Marti-Masso, G De La Meilleure, N. Mullatti, M. Rodegher, N. C. Notermans, T. A. T. Warner, S. Aktan, J. P. Louboutin, L. Volpe, C. Scheidt, W. Aust, C. M. Wiles, U. Schneider, S. K. Braekken, W. R. Willems, K. Usuku, Peter M. Rothwell, C. Talamon, M. L. Sacchetti, A. Codina, M. H. Marion, A. Santoro, J. Roda, A. Bordoni, D. J. Taylor, S. Ertas, H. H. Emmen, J. Vichez, V. BesanÇon, R. E. Passingham, M. L. Malosio, A. Vérier, M. Bamberg, A. W. Hansen, E. Mostacero, G. Gaudriault, Marie Vidailhet, B. Birebent, K. Strijckmans, F. Giannini, T. Kammer, I. Araujo, J. Nowicki, E. Nikolov, A. Hutzelmann, R. Gherardi, J. Verroust, L. Austoni, A. Scheller, A. Vazquez, S. Matheron, H. Holthausen, J. M. Gerard, M. Bataillard, S. Dethy, V. H. Patterson, V. Ivanez, N. P. Hirsch, F. Ozer, M. Sutter, C. Jacomet, M. Mora, Bruno Colombo, A. Sarropoulos, T. H. Papapetropoulos, M. Schwarz, D. S. Dinner, N. Acarin, B. Iandolo, J. O. Riis, P. R. J. Barnes, F. Taroni, J. Kazenwadel, L. Torre, A. Lugaresi, I. L. Henriques, S. Pauli, S. Alfonso, Pedro Quesada, A. S. T. Planting, J. M. Castilla, Thomas Gasser, M. Van der Linden, A. Alfaro, E. Nobile-Orazio, G. Popova, W. Vaalburg, F. G. A. van der Mech, L. Williams, F. Medina, J. P. Vernant, J. Yaouanq, B. Storch-Hagenlocher, A. Potemkowski, R. Riva, M. H. Mahagne, M. Ozturk, Ve. Drory, N. Konic, C. Jungreis, A. Pou Serradell, J. L. Gauvrit, G. J. Chelune, S. Hermandez, T. Dingus, L. Hewer, Ch. Koch, M. N. Metz-Lutz, G. Parlato, M. Sinaki, Charles Pierrot-Deseilligny, H. C. Diener, J. Broeckx, J. Weill-Fulazza, M. L. Villar, M. Rizzo, O. Ganslandt, C. Duran, N. A. Fletcher, G. Di Giovacchino, Susan T. Iannaccone, C. Kolig, N. Fabre, H. A. Crockard, Rita Bella, M. Tazir, E. Papagiannuli, K. Overgaard, Emma Ciafaloni, I. Lorenzetti, F. Viader, P. A. H. Millac, I. Montiel, L. H. Visser, M. Palomar, P. L. Murgia, H. Pedersen, Rafael Blesa, S. Seddigh, W. O. Renier, I. Lemahieu, H. M. L. Jansen, L. Rosin, J. Galofre, K. Mattos, M. Pondal, G. M. Hadjigeorgiou, D. Francis, L. Cantin, D. Stegeman, M. Rango, A. B. M. F. Karim, S. Schraff, B. Castellotti, I. Iriarte, E. Laborde, T. J. Tjan, R. Mutani, D. Toni, B. Bergaasco, J. G. Young, C. Klotzsch, A. Zincone, X. Ducrocq, M. Uchuya, O. J. Kolar, A. Quattrone, T. Bauermann, Nereo Bresolin, J. Vallée, B. C. Jacobs, A. Campos, Werner Poewe, J. A. Villanueva, A. W. Kornhuber, A. Malafosse, E. Diez-Tejedor, G. Jungreia, M. J. A. Puchner, A. Komiyama, O. Saribas, V. Volpini, L. Geremia, S. Bressi, A. Nibbio, Timothy E. Bates, T. z. Tzonev, E. Ideman, G. A. Damlacik, G. Martino, G. Crepaldi, T. Martino, Kjell Någren, E. Idiman, D. Samuel, J. M. Perez Trullen, Y. van der Graaf, J. O. Thorell, M. J. M. Dupuis, E. Sieber, R. D'Alessandro, C. Cazzaniga, J. Faiss, A. Tanguy, A. Schick, I. Hoksergen, A. Cardozo, R. Shakarishvili, G. K. Wennlng, J. L. Marti-Vilalta, J. Weissenbach, I. L. Simone, Amalia C. Bruni, Darius J. Adams, C. Weiller, A. Pietrangeli, F. Croria, C. Vigo-Pelfrey, Patricia Limousin, A. Ducros, G. Conti, O. Lindvall, E. Richter, M. Zuffi, A. Nappo, T. Riise, J. Wijdenes, M. J. Fernandez, J. Rosell, P. Vermersh, S. Servidei, M. S. C. Verdugo, F. Gouttiere, W. Solbach, M. Malbezin, I. S. Watanabe, A. Tumac, W. I. McDonald, D. A. Butterfield, P. P. Costa, F. deRino, F. Bamonti, J. M. Cesar, C. H. Lahoz, I. Mosely, M. Starck, M. H. Lemaitre, K. M. Stephan, S. Tex, R. Bokonjic, I. Mollee, L. Pastena, M. Gutierrez, F. Boiler, M. C. Martinez-Para, M. Velicogna, O. Obuz, A. Grinspan, M. Guarino, L. M. Cartier, E. Ruiz, D. Gambi, S. Messina, M. Villa, Michael G. Hanna, J. Valk, Leone Pascual, M. Clanet, Z. Argov, B. Ryniewicz, E. Magni, B. Berlanga, K. S. Wong, C. Gellera, C. Prevost, F. Gonzalez-Huix, R. Petraroli, J. E. G. Benedikz, I. Kojder, C. Bommelaer, L. Perusse, M. R. Bangioanni, Guy M. McKhann, A. Molina, C. Fresquet, E. Sindern, Florence Pasquier, M. J. Rosas, M. Altieri, O. Simoncini, M. Koutroumanidis, C. A. F. Tulleken, M. Dary-Auriol, S. Oueslati, H. Kruyer, I. Nishisho, C. R. Horning, A. Vital, G. V. Czettritz, J. Ph. Neau, B. Mihout, A. Ameri, M. Francis, S. Quasthoff, D. Taussig, S. Blunt, P. Valentin, C. Y. Gao, O. Heinzlef, H. d'Allens, C. Coudero, M. Erfas, G. Borghero, P. J. Modrego Pardo, M. C. Patrosso, N. L. Gershfeld, P. A. J. M. Boon, O. Sabouraud, M. Lara, J. Svennevig, G. L. Lenzi, A. Barrio, H. Villaroya, JosÇ M. Manubens, O. Boespflug-Tanguy, M. Carreras, D. A. Costiga, J. P. Breux, S. Lynn, C. Oliveras Ley, A. G. Herbaut, J. Nos, C. Tornali, Y. A. Hekster, J. L. Chopard, J. M. Manubens, P. Chemouilli, A. Jovicic, F. Dworzak, S. Smirne, S. E. Soudain, B. Gallano, D. Lubach, G. Masullo, G. Izquierdo, A. Pascual Leone Pascual, A. Sessa, V. Freitas, O. Crambes, L. Ouss, G. W. Van Dijk, P. Marchettini, P. Confalonieri, M. Donaghy, A. Munnich, M. Corbo, and M. E. L. van der Burg

Subjects
Neurology, business.industry, Media studies, Library science, Medicine, Neurology (clinical), business
Published
1994
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11. Striatonigral degeneration with neurofibrillary tangles

Author

K. Renkawek and M. W. I. M. Horstink

Subjects
Adult, Pathology, medicine.medical_specialty, Striatonigral Degeneration, Autopsy, Degeneration (medical), Pathology and Forensic Medicine, Progressive supranuclear palsy, Central nervous system disease, Cellular and Molecular Neuroscience, Degenerative disease, medicine, Humans, Pathological, Movement Disorders, business.industry, Neurofibrillary Tangles, Parkinson Disease, Neurofibrillary tangle, Organ Size, medicine.disease, Magnetic Resonance Imaging, Corpus Striatum, Substantia Nigra, Female, Supranuclear Palsy, Progressive, Neurology (clinical), business
Abstract

An autopsy was performed on a 48-year-old woman with clinical features of parkinsonism-plus syndrome with dominating akinesia. Neuropathological examination revealed striato-nigral degeneration (SND) and neurofibrillary tangles (NFT) characterizing progressive supranuclear palsy. Such an unusual combination of pathological findings may constitute a distinct clinico-pathological entity, with akinesia as the main clinical symptom, and with a pathological substrate of SND and NFT. We suggest that such cases may establish a separate variant within multisystem atrophies syndromes.

Published
1993
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12. Clinical efficacy of sinemet CR 50/200 versus sinemet 25/100 in patients with fluctuating parkinson's disease

Author

E.C. Wolters, M. W. I. M. Horstink, E. N. H. Jansen, and R. A. C. Roos

Subjects
medicine.medical_specialty, Levodopa, Parkinson's disease, business.industry, Urology, General Medicine, medicine.disease, Surgery, law.invention, Clinical trial, Tolerability, Randomized controlled trial, law, Statistical significance, medicine, In patient, Neurology (clinical), business, Sinemet CR, medicine.drug
Abstract

In a multicenter study we selected 84 patients with fluctuating Parkinson's disease in order to evaluate the effects of controlled-release Sinemet 50/200 (=CR) versus standard Sinemet 25/100 (=STD) in an open-label 8-week titration period, followed by a double-blind, double-dummy 24-week treatment period. In contrast with previous double-blind studies, the efficacy of Sinemet CR proved to be significantly superior to that of Sinemet-STD according to NYUPDS and NUDS rating scales. This higher efficacy of Sinemet CR was not achieved at the expense of safety and/or tolerability. Actual total daily levodopa dosage in patients treated with Sinemet CR was increased by 33%; however, the plasma level of this dosage is calculated to be similar to that of the previous dosage of Sinemet-STD (bio-availability of Sinemet CR is 71%). Mean numbers of daily doses, off-hours, and off-periods were decreased significantly during Sinemet CR treatment. Although all other variables suggest that the number of on-hours had to be increased, statistical significance could not be reached in this respect.

Published
1992
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13. PARKINSON'S DISEASE AND PARKINSONISM IN THE ELDERLY

Author

M. W. I. M. Horstink

Subjects
Geriatrics, medicine.medical_specialty, Rehabilitation, Parkinson's disease, Neurology, Essential tremor, business.industry, medicine.medical_treatment, Parkinsonism, education, Disease, medicine.disease, humanities, nervous system diseases, body regions, Normal pressure hydrocephalus, medicine, Neurology (clinical), Psychiatry, business
Abstract

The title Parkinson's Disease and Parkinsonism in the Elderly binds the authors to a discussion of diagnostic and therapeutic problems of parkinsonism in particular in relation to old age. I therefore considered whether problems typically related to old age were covered by the book and found that this certainly was the case: the second chapter covers the differential diagnosis with vascular parkinsonism, normal pressure hydrocephalus, essential tremor and senile gait; Chapter 9 extensively discusses drug therapy of Parkinson's disease in the elderly, and throughout the book, special reference is made to problems related to old age. The list of contributors includes an even balance of specialists in geriatric medicine, neurology and rehabilitation in the broadest sense. The book can be divided into two parts: eight chapters discuss matters of diagnosis and drug therapy; these are followed by a second part with six chapters on social needs and rehabilitation. I therefore conclude that this book is written for those practically involved in care of the elderly with parkinsonism. The first chapter, by Meara, offers a glossary of terms. Parkinsonism is defined as a clinical syndrome of akinesia accompanied by rigidity and often tremor. I would have preferred the term \`bradykinesia' (slowness of movement) rather than \`akinesia' (loss of movement), because bradykinesia is thought by many to be the hallmark of the hypokinetic-rigid syndrome. A pill-rolling tremor is, however, believed to be \`almost pathognomic' (Chapter 1) or \`very strongly suggests' (Chapter 2) Parkinson's disease, but unfortunately the authors do not provide a reference to substantiate this. Denny Brown ( The Basal Ganglia , 1962) argued that the movement of the thumb against the finger is very typical of Parkinson's disease, but in those days neurologists were not yet aware of a number of parkinsonian syndromes which we now differentiate from Parkinson's disease. More …

Published
2000
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15. Review of the therapeutic management of Parkinson's disease. Report of a joint task force of the European Federation of Neurological Societies (EFNS) and the Movement Disorder Society-European Section (MDS-ES). Part II: late (complicated) Parkinson's disease

Author

M. Horstink, E. Tolosa, U. Bonuccelli, G. Deuschl, A. Friedman, P. Kanovsky, J. P. Larsen, A. Lees, W. Oertel, W. Poewe, O. Rascol, and C. Sampaio

Subjects
Antiparkinson Agents, Movement Disorders, Neurology, Autonomic Nervous System Diseases, Deep Brain Stimulation, Mental Disorders, Humans, Parkinson Disease, Neurology (clinical), Neurosurgical Procedures
Abstract

To provide evidence-based recommendations for the management of late (complicated) Parkinson's disease (PD), based on a review of the literature. Complicated PD refers to patients suffering from the classical motor syndrome of PD along with other motor or non-motor complications, either disease-related (e.g. freezing) or treatment-related (e.g. dyskinesias or hallucinations). MEDLINE, Cochrane Library and INAHTA database literature searches were conducted. National guidelines were requested from all EFNS societies. Non-European guidelines were searched for using MEDLINE. Part II of the guidelines deals with treatment of motor and neuropsychiatric complications and autonomic disturbances. For each topic, a list of therapeutic interventions is provided, including classification of evidence. Following this, recommendations for management are given, alongside ratings of efficacy. Classifications of evidence and ratings of efficacy are made according to EFNS guidance. In cases where there is insufficient scientific evidence, a consensus statement ('good practice point') is made.

Published
2006

16. Erythrocyte Membrane Abnormalities in Neuroacanthocytosis: Evidence for a Neuron-Erythrocyte Axis?

Author

W. J. De Grip, M. W. I. M. Horstink, and Giel J. C. G. M. Bosman

Subjects
biology, Chemistry, medicine.disease, Erythrocyte membrane, Cytosol, medicine.anatomical_structure, Membrane, Neuroacanthocytosis, medicine, biology.protein, Biophysics, sense organs, Neuron, skin and connective tissue diseases, Cell shape, Band 3, Homeostasis
Abstract

There are no indications for the involvement of one specific erythrocyte membrane protein in the formation of acanthocytes in neuroacanthocytosis, with two notable exceptions: the XK protein and the anion exchanger band 3. Changes in structure and/or function of erythrocyte band 3 are consistent findings in patients with neuroacanthocytosis. These changes are probably secondary to other processes, which may include changes in the lipid composition of the erythrocyte membrane. As band 3 is associated with a number of membrane and cytosolic proteins, changes in band 3 not only affect cell shape, but also total cell homeostasis. Elucidation of the disease-related changes in band 3 may be instrumental in the elucidation of the molecular causes of neuroacanthocytosis.

Published
2004
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17. [Dementia with Lewy bodies; 2 patients with exacerbation due to an atypical antipsychotic, but with a favorable response to the cholinesterase inhibitor rivastigmine]

Author

A J T M, Scheepmaker, M W I M, Horstink, W H L, Hoefnagels, and F E, Strijks

Subjects
Aged, 80 and over, Lewy Body Disease, Male, Phenylcarbamates, Rivastigmine, Pirenzepine, Risperidone, Antiparkinson Agents, Levodopa, Benzodiazepines, Neuroprotective Agents, Treatment Outcome, Olanzapine, Humans, Drug Therapy, Combination, Carbamates, Cholinesterase Inhibitors, Aged, Antipsychotic Agents
Abstract

In two patients, men aged 80 and 75 years with cognitive deterioration, hallucinations and parkinsonism, the clinical diagnosis 'dementia with Lewy bodies' was established. Treatment with an atypical antipsychotic, risperidone and olanzapine respectively, resulted in an exacerbation of the parkinsonism. Rivastigmine evidently improved the psychosis, the anxiety and the cognitive, mood and behaviour disorders. Titrated treatment with levodopa improved the mobility without an increase of the psychosis. The treatment of dementia with Lewy bodies is complex. Levodopa can lead to an increase in visual hallucinations. Antipsychotics often cause serious side effects, such as increasing parkinsonism, sedation and cognitive deterioration. Cholinesterase inhibitors such as rivastigmine could possibly provide an alternative treatment for the neuropsychiatric symptoms.

Published
2003

18. P15.02: Tetra-amelia: a case report

Author

I. D. Graaf, I. Tromp, M. Horstink, and M. Elting

Subjects
Reproductive Medicine, Radiological and Ultrasound Technology, business.industry, Obstetrics and Gynecology, Medicine, Radiology, Nuclear Medicine and imaging, Tetra-Amelia, General Medicine, Theology, business
Published
2009
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19. Accurate differentiation of parkinsonism and essential tremor using visual assessment of [

Author

Hani T S, Benamer, Jim, Patterson, Donald G, Grosset, J, Booij, K, de Bruin, E, van Royen, J D, Speelman, M H I M, Horstink, H J W A, Sips, R A, Dierckx, J, Versijpt, D, Decoo, C, Van Der Linden, D M, Hadley, M, Doder, A J, Lees, D C, Costa, S, Gacinovic, W H, Oertel, O, Pogarell, H, Hoeffken, K, Joseph, K, Tatsch, J, Schwarz, and V, Ries

Published
1999

20. Evidence for lateral premotor and parietal overactivity in Parkinson's disease during sequential and bimanual movements. A PET study (a comment)

Author

M. W. I. M. Horstink, Antje S. Meyer, Alexander R. Cools, Dick F. Stegeman, and Peter Praamstra

Subjects
Parkinson's disease, Movement, Brain, Parkinson Disease, medicine.disease, Hand, Frontal Lobe, Neurofysiologische analyse van bewegingsstoornissen ihb de ziekte van Parkinson, Parietal Lobe, medicine, Neurophysiological analysis of movement disorders with emphasis on Parkinson's disease, Humans, Neurology (clinical), Psychology, Neuroscience, Psychomotor Performance, Tomography, Emission-Computed
Abstract

Item does not contain fulltext

Published
1998

21. Backbone dynamics of the major coat protein of bacteriophage M13 in detergent micelles by 15N nuclear magnetic resonance relaxation measurements using the model-free approach and reduced spectral density mapping

Author

Ruud N.H. Konings, C. W. Hilbers, F.J.M. van de Ven, M. L. Remerowski, Lennard M. Horstink, and C.H.M. Papavoine

Subjects
Magnetic Resonance Spectroscopy, Phosphorylcholine, Detergents, Coat protein, Biochemistry, Micelle, Protein Structure, Secondary, Bacteriophage, chemistry.chemical_compound, Nuclear magnetic resonance, Capsid, Sodium dodecyl sulfate, Micelles, biology, Dynamics (mechanics), Relaxation (NMR), Membrane Proteins, Sodium Dodecyl Sulfate, Nuclear magnetic resonance spectroscopy, biology.organism_classification, Crystallography, chemistry, Filamentous bacteriophage, Capsid Proteins, Mathematics, Bacteriophage M13
Abstract

The backbone dynamics of the major coat protein (gVIIIp) of the filamentous bacteriophage M13, solubilized in detergent micelles, have been studied using 15N nuclear magnetic resonance spectroscopy at three frequencies. Motional parameters and overall and internal correlation times were derived with the model-free approach. It was also checked whether these parameters had to be modified due to anisotropic motion of the protein/micelle complex. Reduced spectral density mapping was used to calculate the spectral densities at J(O), J(omegaN), and [J(omegaH)]. The spectral densities were interpreted by mapping a linear or scaled linear combination of two Lorentzians onto a J(O)-J(omega) plot. The major coat protein of bacteriophage M13 consists of two alpha-helices, one of which is hydrophobic and located within the micelle, while the other is amphipathic and located on the surface of the micelle. Our results indicate that the motion of the hydrophobic helix is restricted such that it corresponds to the overall tumbling of the protein/micelle complex. The interpretation of the relaxation data of the amphipathic helix by means of the model-free approach and the reduced spectral density mapping indicate that in addition to the overall motion all residues in this helix are subject to motion on the fast nanosecond and picosecond time scales. The motions of the vectors in the low nanosecond range are characterized by similar values of the spectral densities and correlation times and represent the motion of the amphipathic helix on and away from the surface of the micelle. The relaxation data of the residues in the hinge region connecting the helices show that there is an abrupt change from highly restricted to less restricted motion. Both the C-terminal and N-terminal residues are very mobile.

Published
1997

22. Idiopathic spasmodic torticollis: a survey of the clinical syndromes and patients' experiences

Author

T.W. van Weerden, C.A.L. Hoogduin, M. W. I. M. Horstink, R.A.C. Roos, H.W.M. Anten, J.D. Speelman, G.M.F.M. van Herwaarden, J.U.R. Niewold, and Other departments

Subjects
Adult, Male, medicine.medical_specialty, Psychometrics, Adolescent, Spasmodic Torticollis, Neurological disorder, Cholinergic Antagonists, Drug treatment, Benzodiazepines, Clinical investigation, Surveys and Questionnaires, Patient experience, medicine, Humans, Cervical dystonia, Physical Therapy Modalities, Torticollis, business.industry, General Medicine, Middle Aged, medicine.disease, Antidepressive Agents, Physical therapy, Surgery, Female, Neurology (clinical), business, Psychosocial, Antipsychotic Agents
Abstract

We evaluated the medical and psychosocial experiences of 59 patients with idiopathic spasmodic torticollis (ST) by means of a structured questionnaire. The results generally corresponded with those of other studies in the literature. Diagnosis is delayed in many patients, and ST negatively influences the patients' social lives. Because drug treatment and physiotherapy are only of sufficient value in a minority, most patients seek benefit from numerous other therapies, none of which has been shown to improve ST.

Published
1994

23. Erythrocyte anion transporter and antibrain immunoreactivity in chorea-acanthocytosis. A contribution to etiology, genetics, and diagnosis

Author

W.J. de Grip, I.G.P. Bartholomeus, M. W. I. M. Horstink, and Giel J. C. G. M. Bosman

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Immunoblotting, Acanthocytes, Acanthocytosis, Degenerative disease, Chorea, Internal medicine, Anion Exchange Protein 1, Erythrocyte, medicine, Humans, Band 3, Chorea acanthocytosis, biology, General Neuroscience, Erythrocyte Membrane, Brain, Membrane transport, medicine.disease, Blood Protein Electrophoresis, Sulfate transport, Ion Exchange, Red blood cell, Endocrinology, medicine.anatomical_structure, biology.protein, Female, medicine.symptom
Abstract

Novel structural and functional alterations in the erythrocyte anion transporter band 3 are described in one patient with definite, and in two patients with symptoms compatible with chorea-acanthocytosis, but without acanthocytes. Immunoblotting analysis shows increased fragmentation of band 3, and sulfate flux measurements indicate that anion transport activity is reduced in the erythrocytes of these patients. These changes are similar, but not identical to those observed during normal erythrocyte aging. In addition, distinct antibrain immunoreactivity was present in the plasma of these patients. A family study indicates that abnormal erythrocyte band 3 structure and function and antibrain immunoreactivity may be phenotypes of two independent, genetically determined factors, that are part of the heterogenic defect of chorea-acanthocytosis. The findings in the patients without acanthocytes indicate that the biochemical abnormalities may be related to a chorea-acanthocytosis-like, amyotrophic extrapyramidal movement disorder with axonal neuropathy. Measurement of erythrocyte sulfate transport and plasma antibrain immunoreactivity could be of use in establishing the diagnosis and further unravelling the genetic background of choreaacanthocytosis and related syndromes.

Published
1994

24. Short-term memory in Parkinson's disease after withdrawal of long-term anticholinergic therapy

Author

M. W. I. M. Horstink, G. van Herwaarden, and H. J. C. Berger

Subjects
Male, Levodopa, Parkinson's disease, Time Factors, medicine.drug_class, Short-term memory, Motor Activity, Motor function, Drug Administration Schedule, Paired associate, Anticholinergic, Medicine, Humans, Pharmacology (medical), Anticholinergic Drugs, Aged, Pharmacology, Memory Disorders, business.industry, Parasympatholytics, Parkinson Disease, Middle Aged, medicine.disease, Substance Withdrawal Syndrome, Memory, Short-Term, Anesthesia, Feasibility Studies, Female, Neurology (clinical), business, medicine.drug
Abstract

We assessed the short-term memory (STM) using the Visual Paired Associates and the Verbal Paired Associates test, and the motor status at the end of 7.8 +/- 3.7 years of anticholinergic therapy in 22 nondemented patients with Parkinson's disease (PD). Eighteen patients managed to stop anticholinergic therapy. During anticholinergic therapy, STM in PD is significantly worse than in normal controls (CS). Two months after the withdrawal of anticholinergic drugs, the STM retest gain is significantly greater in PD than in CS, and at that time STM in PD did equal CS levels. After withdrawal of anticholinergic therapy, thirteen patients noticed a deterioration of motor function; the dose of levodopa had to be increased in seven patients. We conclude that in nondemented PD patients, long-term anticholinergic therapy probably does not result in irreversible damage to STM, and withdrawal of long-term anticholinergic therapy is feasible in the majority of PD patients.

Published
1993

25. Variants of Nijmegen breakage syndrome and ataxia telangiectasia

Author

C M, Weemaes, D F, Smeets, M, Horstink, A, Haraldsson, and J A, Bakkeren

Subjects
Adult, Chromosomes, Human, Pair 14, Gene Rearrangement, Male, Adolescent, T-Lymphocytes, Genetic Variation, Syndrome, Radiation Tolerance, Ataxia Telangiectasia, Immunoglobulin M, Humans, Female, alpha-Fetoproteins, Chromosomes, Human, Pair 7
Abstract

Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by telangiectasia, progressive ataxia, sinopulmonary infections and a combined immunodeficiency (usually consisting of IgA deficiency, IgE deficiency, IgG2 and IgG4 deficiency and a disturbed T cell immunity). The alpha-fetoprotein level is elevated. Cytogenetic studies reveal a very specific chromosome instability with multiple chromosome 7 and/or 14 rearrangements (preferential breakpoints 14q32, 14q12, 7q35 and 7p12). X-ray hypersensitivity is one of the hallmarks of the disease. Nijmegen Breakage Syndrome (NBS), an autosomal recessive disorder with some features of AT, was first reported in 1981. At this moment at least 19 patients have been recognized. Clinical symptoms are microcephaly from birth, a peculiar face, growth retardation, repeated respiratory tract infections and renal abnormalities. Immunological, cytogenetic and cell-biological findings in NBS are identical to AT. However, alpha-fetoprotein levels are not increased. A tendency toward malignancy has been demonstrated in both syndromes. Recently, we encountered three patients with variants of these syndromes.

Published
1993

27. Parkinsonism due to a subdural hematoma

Author

M. W. I. M. Horstink and A. T. M. Hageman

Subjects
medicine.medical_specialty, business.industry, Parkinsonism, MEDLINE, medicine.disease, Surgery, Chronic disease, Hematoma, Neurology, X ray computed, medicine, Etiology, Neurology (clinical), business
Published
1994
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28. How much phenotypic variation can be attributed to parkin genotype?

Author

Ebba Lohmann, Magali Periquet, Vincenzo Bonifati, Nick W. Wood, Giuseppe De Michele, Anne-Marie Bonnet, Valérie Fraix, Emmanuel Broussolle, Martin W. I. M. Horstink, Marie Vidailhet, Patrice Verpillat, Thomas Gasser, David Nicholl, Hélio Teive, Salmo Raskin, Olivier Rascol, Alain Destée, Merle Ruberg, Francesca Gasparini, and Giuseppe Meco

Published
2003

29. Estrogen as Neuroprotectant of Nigrostriatal Dopaminergic System: Laboratory and Clinical Studies.

Author

Dean E. Dluzen and Martin W. I. M. Horstink

Abstract

In this review, we relate both laboratory and clinical evidence associated with the capacity for estrogen to function as a modulator of nigrostriatal dopaminergic pathology. To accomplish this goal, we have divided this review into three parts. In Part 1, we provide a brief historical perspective of studies that have laid the groundwork for demonstrating the existence of hormonal- nigrostriatal interactions. In Part 2, we focus specifically on laboratory data that show the ability and conditions by which estrogen may function as a neuroprotectant of the nigrostriatal dopaminergic system. Finally, in Part 3, we review the clinical literature related to this issue as a means for consideration of estrogen as a modulator, neuroprotectant, and therapy for Parkinson disease. [ABSTRACT FROM AUTHOR]

Published
2003
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30. Morphology of the cervical spinal cord on computed myelography

Author

E. Meijer, M. W. M. Horstink, A. Keyser, and H. O. M. Thijssen

Subjects
Adult, Male, medicine.medical_specialty, Neurology, Normal values, chemistry.chemical_compound, Atrophy, Metrizamide, medicine, Humans, Radiology, Nuclear Medicine and imaging, Kyphosis, Spinal Cord Neoplasms, Myelography, Neuroradiology, medicine.diagnostic_test, business.industry, Anatomy, Middle Aged, medicine.disease, Spinal cord, medicine.anatomical_structure, Scoliosis, Spinal Cord, chemistry, Female, Neurology (clinical), Neurosurgery, Radiology, Tomography, X-Ray Computed, Cardiology and Cardiovascular Medicine, business, Spinal Canal
Abstract

To ensure adequate use of the technique of computed myelography (CM) it is necessary to have an exact picture of the morphology of the normal spinal cord as demonstrated by this technique. This has been obtained by studying the morphology and measuring the frontal and sagittal diameter of the cervical cord in 20 patients. The normal values are presented. The changes of this morphology in one patient with a tumour, one patient with atrophy of the spinal cord and in some patients with congenital malformations are also reported.

Published
1979
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31. Review of the therapeutic management of Parkinson's disease. Report of a joint task force of the European Federation of Neurological Societies and the Movement Disorder Society-European Section. Part I: early (uncomplicated) Parkinson's disease.

Author

Horstink M, Tolosa E, Bonuccelli U, Deuschl G, Friedman A, Kanovsky P, Larsen JP, Lees A, Oertel W, Poewe W, Rascol O, and Sampaio C

Subjects
Antiparkinson Agents therapeutic use, Disease Progression, Evidence-Based Medicine, Humans, Neuroprotective Agents therapeutic use, Occupational Therapy, Parkinson Disease drug therapy, Parkinson Disease physiopathology, Parkinsonian Disorders drug therapy, Physical Therapy Modalities, Speech Therapy, Parkinson Disease therapy
Abstract

The aim of the study was to provide evidence-based recommendations for the management of early (uncomplicated) Parkinson's disease (PD), based on a review of the literature. Uncomplicated PD refers to patients suffering from the classical motor syndrome of PD only, without treatment-induced motor complications and without neuropsychiatric or autonomic problems. MEDLINE, Cochrane Library and International Network of Agencies for Health Technology Assessment (INAHTA) database literature searches were conducted. National guidelines were requested from all European Federation of Neurological Societies (EFNS) societies. Non-European guidelines were searched for using MEDLINE. Part I of the guidelines deals with prevention of disease progression, symptomatic treatment of motor features (parkinsonism), and prevention of motor and neuropsychiatric complications of therapy. For each topic, a list of therapeutic interventions is provided, including classification of evidence. Following this, recommendations for management are given, alongside ratings of efficacy. Classifications of evidence and ratings of efficacy are made according to EFNS guidance. In cases where there is insufficient scientific evidence, a consensus statement (good practice point) is made.

Published
2006
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32. Review of the therapeutic management of Parkinson's disease. Report of a joint task force of the European Federation of Neurological Societies (EFNS) and the Movement Disorder Society-European Section (MDS-ES). Part II: late (complicated) Parkinson's disease.

Author

Horstink M, Tolosa E, Bonuccelli U, Deuschl G, Friedman A, Kanovsky P, Larsen JP, Lees A, Oertel W, Poewe W, Rascol O, and Sampaio C

Subjects
Antiparkinson Agents therapeutic use, Autonomic Nervous System Diseases etiology, Deep Brain Stimulation, Humans, Mental Disorders drug therapy, Mental Disorders etiology, Movement Disorders drug therapy, Movement Disorders etiology, Movement Disorders physiopathology, Neurosurgical Procedures, Autonomic Nervous System Diseases drug therapy, Mental Disorders therapy, Movement Disorders therapy, Parkinson Disease complications, Parkinson Disease psychology
Abstract

To provide evidence-based recommendations for the management of late (complicated) Parkinson's disease (PD), based on a review of the literature. Complicated PD refers to patients suffering from the classical motor syndrome of PD along with other motor or non-motor complications, either disease-related (e.g. freezing) or treatment-related (e.g. dyskinesias or hallucinations). MEDLINE, Cochrane Library and INAHTA database literature searches were conducted. National guidelines were requested from all EFNS societies. Non-European guidelines were searched for using MEDLINE. Part II of the guidelines deals with treatment of motor and neuropsychiatric complications and autonomic disturbances. For each topic, a list of therapeutic interventions is provided, including classification of evidence. Following this, recommendations for management are given, alongside ratings of efficacy. Classifications of evidence and ratings of efficacy are made according to EFNS guidance. In cases where there is insufficient scientific evidence, a consensus statement ('good practice point') is made.

Published
2006
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33. Clinical features and neuroimaging of PARK7-linked parkinsonism.

Author

Dekker M, Bonifati V, van Swieten J, Leenders N, Galjaard RJ, Snijders P, Horstink M, Heutink P, Oostra B, and van Duijn C

Subjects
Adult, Chromosomes, Human, Pair 1, Consanguinity, Corpus Striatum pathology, Corpus Striatum physiopathology, Disease Progression, Female, Genetic Carrier Screening, Humans, Intracellular Signaling Peptides and Proteins, Male, Middle Aged, Nerve Net diagnostic imaging, Netherlands, Neurologic Examination, Pedigree, Protein Deglycase DJ-1, Radionuclide Imaging, Substantia Nigra pathology, Substantia Nigra physiopathology, Chromosome Mapping, Diagnostic Imaging, Oncogene Proteins genetics, Parkinsonian Disorders diagnosis, Parkinsonian Disorders genetics, Phenotype
Abstract

We recently reported linkage to chromosome 1p36 (the PARK7-locus) in a family with early-onset parkinsonism. Linkage to this locus has since been confirmed in an independent data set. We describe clinical and neuroimaging features of the 4 patients in the original PARK7-linked kindred. Age at onset of parkinsonism varied from 27 to 40 years. Clinical progression was slow, and response to dopaminergic therapy good. The clinical spectrum ranged from mild hypokinesia and rigidity, to severe parkinsonism with levodopa-induced dyskinesias and motor fluctuation. Three of four patients with PARK7-linked parkinsonism exhibited psychiatric disturbances. Structural neuroimaging was unremarkable, but functional imaging of the brain, carried out in 3 patients, showed significant evidence for a presynaptic dopamine deficit, and assessment of cerebral glucose metabolism, as carried out in 1 patient, showed possible cerebellar involvement., (Copyright 2003 Movement Disorder Society)

Published
2003
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34. Estrogen as neuroprotectant of nigrostriatal dopaminergic system: laboratory and clinical studies.

Author

Dluzen D and Horstink M

Subjects
Basal Ganglia Diseases prevention & control, Humans, Neostriatum cytology, Neostriatum drug effects, Parkinson Disease pathology, Parkinson Disease prevention & control, Sex Characteristics, Substantia Nigra cytology, Substantia Nigra drug effects, Dopamine physiology, Estrogens pharmacology, Neostriatum physiology, Neuroprotective Agents, Substantia Nigra physiology
Abstract

In this review, we relate both laboratory and clinical evidence associated with the capacity for estrogen to function as a modulator of nigrostriatal dopaminergic pathology. To accomplish this goal, we have divided this review into three parts. In Part 1, we provide a brief historical perspective of studies that have laid the groundwork for demonstrating the existence of hormonal- nigrostriatal interactions. In Part 2, we focus specifically on laboratory data that show the ability and conditions by which estrogen may function as a neuroprotectant of the nigrostriatal dopaminergic system. Finally, in Part 3, we review the clinical literature related to this issue as a means for consideration of estrogen as a modulator, neuroprotectant, and therapy for Parkinson disease.

Published
2003
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35. Posttraumatic tremor without parkinsonism in a patient with complete contralateral loss of the nigrostriatal pathway.

Author

Zijlmans J, Booij J, Valk J, Lees A, and Horstink M

Subjects
Adult, Corpus Striatum blood supply, Electromyography, Hand physiopathology, Humans, Magnetic Resonance Imaging, Male, Muscle, Skeletal physiopathology, Neural Pathways blood supply, Substantia Nigra blood supply, Tomography, Emission-Computed, Single-Photon, Tremor diagnosis, Tremor physiopathology, Brain Injuries complications, Brain Injuries pathology, Corpus Striatum pathology, Neural Pathways pathology, Substantia Nigra pathology, Tremor etiology
Abstract

We present a patient with posttraumatic tremor who did not show any [(123)I]FP-CIT uptake in the contralateral putamen and caudate. The absence of hypokinesia and rigidity is surprising in the presence of a striatal dopaminergic denervation that is even more severe than in Parkinson's disease. An explanation, therefore, could be that the lesion in the subthalamic nucleus in our patient prevented the onset of a Parkinson syndrome., (Copyright 2002 Movement Disorder Society)

Published
2002
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36. Park7, a novel locus for autosomal recessive early-onset parkinsonism, on chromosome 1p36.

Author

van Duijn CM, Dekker MC, Bonifati V, Galjaard RJ, Houwing-Duistermaat JJ, Snijders PJ, Testers L, Breedveld GJ, Horstink M, Sandkuijl LA, van Swieten JC, Oostra BA, and Heutink P

Subjects
Age of Onset, Chromosome Mapping, Female, Humans, Male, Molecular Sequence Data, Pedigree, Chromosomes, Human, Pair 1, Ligases genetics, Parkinsonian Disorders genetics, Ubiquitin-Protein Ligases
Abstract

Although the role of genetic factors in the origin of Parkinson disease has long been disputed, several genes involved in autosomal dominant and recessive forms of the disease have been localized. Mutations associated with early-onset autosomal recessive parkinsonism have been identified in the Parkin gene, and recently a second gene, PARK6, involved in early-onset recessive parkinsonism was localized on chromosome 1p35-36. We identified a family segregating early-onset parkinsonism with multiple consanguinity loops in a genetically isolated population. Homozygosity mapping resulted in significant evidence for linkage on chromosome 1p36. Multipoint linkage analysis using MAPMAKER-HOMOZ generated a maximum LOD-score of 4.3, with nine markers spanning a disease haplotype of 16 cM. On the basis of several recombination events, the region defining the disease haplotype can be clearly separated, by > or =25 cM, from the more centromeric PARK6 locus on chromosome 1p35-36. Therefore, we conclude that we have identified on chromosome 1 a second locus, PARK7, involved in autosomal recessive, early-onset parkinsonism.

Published
2001
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37. Origin of the mutations in the parkin gene in Europe: exon rearrangements are independent recurrent events, whereas point mutations may result from Founder effects.

Author

Periquet M, Lücking C, Vaughan J, Bonifati V, Dürr A, De Michele G, Horstink M, Farrer M, Illarioshkin SN, Pollak P, Borg M, Brefel-Courbon C, Denefle P, Meco G, Gasser T, Breteler MM, Wood N, Agid Y, and Brice A

Subjects
Age of Onset, Chromosome Mapping, Europe, Family, Genes, Recessive, Genetic Markers, Humans, Linkage Disequilibrium, Microsatellite Repeats genetics, Nuclear Family, Point Mutation, Sequence Deletion, Ubiquitin-Protein Ligases, Chromosomes, Human, Pair 6, Exons, Founder Effect, Gene Rearrangement, Ligases genetics, Mutation, Parkinson Disease genetics, Parkinsonian Disorders genetics, White People genetics
Abstract

A wide variety of mutations in the parkin gene, including exon deletions and duplications, as well as point mutations, result in autosomal recessive early-onset parkinsonism. Interestingly, several of these anomalies were found repeatedly in unrelated patients and may therefore result from recurrent, de novo mutational events or from founder effects. In the present study, haplotype analysis, using 10 microsatellite markers covering a 4.7-cM region known to contain the parkin gene, was performed in 48 families, mostly from European countries, with early-onset autosomal recessive parkinsonism. The patients carried 14 distinct mutations in the parkin gene, and each mutation was detected in more than one family. Our results support the hypothesis that exon rearrangements occurred independently, whereas some point mutations, found in families from different geographic origins, may have been transmitted by a common founder.

Published
2001
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38. Variants of Nijmegen breakage syndrome and ataxia telangiectasia.

Author

Weemaes CM, Smeets DF, Horstink M, Haraldsson A, and Bakkeren JA

Subjects
Adolescent, Adult, Ataxia Telangiectasia immunology, Chromosomes, Human, Pair 14, Chromosomes, Human, Pair 7, Female, Gene Rearrangement, Genetic Variation, Humans, Immunoglobulin M deficiency, Male, Radiation Tolerance genetics, Syndrome, T-Lymphocytes immunology, alpha-Fetoproteins metabolism, Ataxia Telangiectasia genetics
Abstract

Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by telangiectasia, progressive ataxia, sinopulmonary infections and a combined immunodeficiency (usually consisting of IgA deficiency, IgE deficiency, IgG2 and IgG4 deficiency and a disturbed T cell immunity). The alpha-fetoprotein level is elevated. Cytogenetic studies reveal a very specific chromosome instability with multiple chromosome 7 and/or 14 rearrangements (preferential breakpoints 14q32, 14q12, 7q35 and 7p12). X-ray hypersensitivity is one of the hallmarks of the disease. Nijmegen Breakage Syndrome (NBS), an autosomal recessive disorder with some features of AT, was first reported in 1981. At this moment at least 19 patients have been recognized. Clinical symptoms are microcephaly from birth, a peculiar face, growth retardation, repeated respiratory tract infections and renal abnormalities. Immunological, cytogenetic and cell-biological findings in NBS are identical to AT. However, alpha-fetoprotein levels are not increased. A tendency toward malignancy has been demonstrated in both syndromes. Recently, we encountered three patients with variants of these syndromes.

Published
1993

39. Is levodopa harmful?

Author

Arts N, van de Vlasakker C, Tacke T, and Horstink M

Subjects
Aged, Aged, 80 and over, Female, Humans, Long-Term Care, Male, Middle Aged, Dyskinesia, Drug-Induced etiology, Levodopa adverse effects, Parkinson Disease drug therapy
Published
1991
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40. Hypertrophy of peripheral nerves in the syndrome of multiple mucosal neuromas, endocrine tumours and Marfanoid habitus. Autonomic disturbances and sural nerve findings.

Author

Joosten E, Gabreëls-Festen A, Horstink M, Gabreëls F, Jaspar H, Korten J, and Vingerhoets H

Subjects
Adolescent, Axons ultrastructure, Demyelinating Diseases pathology, Female, Histocytochemistry, Humans, Hypertrophy, Microscopy, Electron, Nerve Degeneration, Nerve Endings, Nerve Fibers, Myelinated ultrastructure, Nerve Regeneration, Syndrome, Dysautonomia, Familial pathology, Marfan Syndrome pathology, Neuroma pathology, Spinal Nerves pathology, Sural Nerve pathology, Thyroid Neoplasms pathology
Published
1974
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