Muskeldystrophien

Zusammenfassung

Hintergrund: Wittmaack berichtet Anfang dieses Jahrhunderts über ein Einfalten (Retraktion) der membranösen Wände der Endolymphräume, die jedoch von anderen Autoren als Artefakt der histologischen Aufarbeitung gedeutet wird. Die genaue Bedeutung dieses Befundes ist bisher nicht bekannt.

Methode: Es wurden die folgenden Sammlungen untersucht: 1. Die Wittmaack-Sammlung in Hamburg. Basierend auf der Originalarbeit von Wittmaack aus dem Jahre 1929 wurden die 67 Felsenbeine der 59 Patienten (0 - 92 Jahre, Mittelwert 35,2 Jahre) erneut einer kritischen Analyse unterzogen und lichtmikroskopisch auf eine Retraktion der endolymphatischen Membranen untersucht. 2. Um altersbedingte Veränderungen auszuschließen, wurden die erhobenen Befunde mit 125 Felsenbeinen von 73 Kindern im Alter von 0 bis 10 Jahre (Durchschnittsalter 13,4 Monate, Median 1,4 Monate) aus der Felsenbeinsammlung der Tufts University, School of Medicine, USA verglichen. Das Einfalten der Reissnerschen Membran in Richtung Stria vascularis und Lamina spirales ossea wurde in leicht-, mittel- und schwergradig unterteilt. Befunde im Sacculus, Utriculus und der Bogengänge wurden ebenfalls dokumentiert.

Ergebnisse: Die Reevaluation der von Wittmaack beschriebenen Präparate zeigt in 81 % eine Retraktion der Reissnerschen Membran im Vergleich zu 33 % in der Tufts Collection. Dort fand sich im Vergleich zu dem hohen Anteil einer cochleären Retraktion nur in 12 % ein sakkulärer und in 4 % ein utrikulärer Kollaps. In der Wittmaack-Sammlung zeigte sich kein signifikanter Unterschied zwischen den zugrunde liegenden Krankheiten. In der Tufts-Sammlung wiesen Kinder, die an extracochleären Infektionen erkrankt waren oder ototoxische Medikamente erhalten hatten, eine signifikant höhere Inzidenz einer Retraktion auf.

Schlussfolgerung: Unsere Ergebnisse deuten darauf hin, dass eine geringgradige Retraktion physiologisch bzw. auch präparationsbedingt zu sein scheint. Dagegen ist ein kompletter Kollaps mit Degeneration der umliegenden Zellstrukturen ein relevanter lokaler bzw. regionaler otopathologischer Befund. Die Reevaluation der Originalfelsenbeine aus der Wittmaack-Sammlung ergab, dass es sich bei einem Teil der von Wittmaack beschriebenen Veränderungen um die Folge einer viralen Labyrinthitis (virale Infektionen konnten zu Wittmaacks Zeiten noch nicht nachgewiesen werden), der Gabe von ototoxischen Substanzen, Durchblutungsstörungen oder auch genetische Ursachen handeln könnte.

Summary

Background: In histologic studies, the volumetric status of the intralabyrinthine fluids is judged by the position of the endolymphatic membranes. Bulging of the membranes, commonly known as endolymphatic hydrops, is assumed to be caused by excess of endolymph. The opposite situation, retraction of the membranes is, however, only incidentally described and relatively little attention has been paid to its significance. Almost one hundred years ago Wittmaack described retraction of the endolymphatic membranes, which has since been considered to be preparation artifact - a concept that essentially remains unchallenged. To test the validity of this long held premise, we examined two sets of temporal bones from different centers.

Material and Methods: We studied the following collections: 1. The Wittmaack collection in Hamburg, Germany. The original material of 67 temporal bones (patient ages 0-92 years, average age 35.2 years) on which Wittmaack based his opinions. 2. For comparison and to exclude age related phenomena, 125 temporal bones from 73 children between the ages newborn to ten years (average age 13.4 months, median 1.5 months) from the temporal bone collection of the Department of Otolaryngology Tufts University School of Medicine. All specimens were studied by light microscopy. Retraction was defined as depression of Reissner's membrane toward the stria vascularis and the Organ of Corti in more than one cochlear turn and was graded into mild, moderate and severe. Additionally the saccule, utricle and semicircular ducts were examined for collapse.

Results: The reevaluation of the 67 temporal bones described by Wittmaack, including those of 7 children below the age of 10 years, showed retraction of Reissner's membrane in 81% compared to 33% of the temporal bones from the Tufts collection. In contrast to the high incidence of retraction in the cochlear duct, fewer saccules (12%) and utricles (4%) were collapsed in the Tufts collection. In the Wittmaack collection no significant differences between the underlying diseases were found, however in the Tufts collection the group of children who suffered from extracochlear infections and malignancies had a higher frequency of retraction.

Conclusion: Mild retraction might be to some extent physiologic or even artifactual. Severe retraction, however, is a definitive finding that is a part of a local or regional otopathologic process. Of material, it is quite possible that Wittmaack's original observations of what he called “hypotonic collapse” was of viral origin (viruses were not known during Wittmaack's time), ototoxicity or even of genetic origin.

Schlüsselwörter

Histopathologie - Kinder - Reissnersche Membrane - Menièresche Krankheit - Virale Labyrinthitis - Ototoxizität

Key words

Histopathology - Children - Viral infection - Reissner's membrane collapse - Labyrinthitis - Ototoxicity - Stria vascularis

Literatur

• 1 Chamberlain J S. Gene therapy of muscular dystrophy.  Hum Mol Genet. 2002;  20 2355-2362
• 2 Skuk D, Vilquin J T, Tremblay J P. Experimental and therapeutic approaches to muscular dystrophies.  Curr Opin Neurol. 2002;  5 563-569
• 3 Walter M C, Lochmuller H. Novel approaches to treat muscular dystrophies.  Expert Opin Investig Drugs. 2001;  4 695-707
• 4 Gollins H, McMahon J, Wells K E, Wells D J. High-efficiency plasmid gene transfer into dystrophic muscle.  Gene Ther. 2003;  6 504-512
• 5 Partridge T. Myoblast transplantation.  Neuromuscul Disord. 2002;  Suppl. S3-S6
• 6 Law P K, Goodwin T G, Fang Q, Duggirala V, Larkin C, Florendo J A, Kirby D S, Deering M B, Li H J, Chen M. Feasibility, safety, and efficacy of myoblast transfer therapy on Duchenne muscular dystrophy boys.  Cell Transplant. 1992;  2 - 3 235-244
• 7 Karpati G, Ajdukovic D, Arnold D, Gledhill R B, Guttmann R, Holland P, Koch P A, Shoubridge E, Spence D, Vanasse M. Myoblast transfer in Duchenne muscular dystrophy.  Ann Neurol. 1993;  1 8-17
• 8 Smythe G M, Hodgetts S I, Grounds M D. Problems and solutions in myoblast transfer therapy.  J Cell Mol Med. 2001;  1 33-47
• 9 Birch J G. Orthopedic management of neuromuscular disorders in children.  Semin Pediatr Neurol. 1998;  2 78-91
• 10 Brooke M H, Fenichel G M, Griggs R C, Mendell J R, Moxley R, Miller J P, Province M A. Clinical investigation in Duchenne dystrophy: 2. Determination of the „power” of therapeutic trials based on the natural history.  Muscle Nerve. 1983;  2 91-103
• 11 Barthelmai W. [On the effect of corticoid administration on creatine phosphokinase in progressive muscular dystrophy].  Verh Dtsch Ges Inn Med. 1965;  71 624-626
• 12 Drachman D B, Toyka K V, Myer E. Prednisone in Duchenne muscular dystrophy.  Lancet. 1974;  7894 1409-1412
• 13 Dubowitz V, Kinali M, Main M, Mercuri E, Muntoni F. Remission of clinical signs in early duchenne muscular dystrophy on intermittent low-dosage prednisolone therapy.  Eur J Paediatr Neurol. 2002;  3 153-159
• 14 Fenichel G M, Florence J M, Pestronk A, Mendell J R, Moxley III R T, Griggs R C, Brooke M H, Miller J P, Robison J, King W. Long-term benefit from prednisone therapy in Duchenne muscular dystrophy.  Neurology. 1991;  12 1874-1877
• 15 Fenichel G M, Mendell J R, Moxley III R T, Griggs R C, Brooke M H, Miller J P, Pestronk A, Robison J, King W, Signore L. A comparison of daily and alternate-day prednisone therapy in the treatment of Duchenne muscular dystrophy.  Arch Neurol. 1991;  6 575-579
• 16 Griggs R C, Moxley III R T, Mendell J R, Fenichel G M, Brooke M H, Pestronk A, Miller J P. Prednisone in Duchenne dystrophy. A randomized, controlled trial defining the time course and dose response. Clinical Investigation of Duchenne Dystrophy Group.  Arch Neurol. 1991;  4 383-388
• 17 Mendell J R, Moxley R T, Griggs R C, Brooke M H, Fenichel G M, Miller J P, King W, Signore L, Pandya S, Florence J. Randomized, double-blind six-month trial of prednisone in Duchenne's muscular dystrophy.  N Engl J Med. 1989;  24 1592-1597
• 18 DeSilva S, Drachman D B, Mellits D, Kuncl R W. Prednisone treatment in Duchenne muscular dystrophy. Long-term benefit.  Arch Neurol. 1987;  8 818-822
• 19 Backman E, Henriksson K G. Low-dose prednisolone treatment in Duchenne and Becker muscular dystrophy.  Neuromuscul Disord. 1995;  3 233-241
• 20 Connolly A M, Schierbecker J, Renna R, Florence J. High dose weekly oral prednisone improves strength in boys with Duchenne muscular dystrophy.  Neuromuscul Disord. 2002;  10 917-925
• 21 Wong B L, Christopher C. Corticosteroids in Duchenne muscular dystrophy: a reappraisal.  J Child Neurol. 2002;  3 183-190
• 22 Bonifati M D, Ruzza G, Bonometto P, Berardinelli A, Gorni K, Orcesi S, Lanzi G, Angelini C. A multicenter, double-blind, randomized trial of deflazacort versus prednisone in Duchenne muscular dystrophy.  Muscle Nerve. 2000;  9 1344-1347
• 23 Reitter B. Deflazacort vs. prednisone in Duchenne muscular dystrophy: trends of an ongoing study.  Brain Dev. 1995;  17 (Suppl.) 39-43
• 24 Mesa L E, Dubrovsky A L, Corderi J, Marco P, Flores D. Steroids in Duchenne muscular dystrophy - deflazacort trial.  Neuromuscul Disord. 1991;  4 261-266
• 25 Folkers K, Simonsen R. Two successful double-blind trials with coenzyme Q10 (vitamin Q10) on muscular dystrophies and neurogenic atrophies.  Biochim Biophys Acta. 1995;  1 281-286
• 26 Ikeda K, Kinoshita M, Iwasaki Y, Wakata N. Creatine monohydrate increases strength in patients with neuromuscular disease.  Neurology. 2000;  2 537
• 27 Walter M C, Lochmuller H, Reilich P, Klopstock T, Huber R, Hartard M, Hennig M, Pongratz D, Muller-Felber W. Creatine monohydrate in muscular dystrophies: A double-blind, placebo-controlled clinical study.  Neurology. 2000;  9 1848-1850
• 28 Louis M, Lebacq J, Poortmans J R, Belpaire-Dethiou M C, Devogelaer J P, Van Hecke P, Goubel F, Francaux M. Beneficial effects of creatine supplementation in dystrophic patients.  Muscle Nerve. 2003;  5 604-610
• 29 Senior K. Duchenne muscular dystrophy improved by gentamicin.  Mol Med Today. 1999;  11 461
• 30 Backman E, Henriksson K G. Treatment of congenital myotonia with sodium selenite and vitamin E.  J Intern Med. 1992;  4 376-377
• 31 Fenichel G M, Brooke M H, Griggs R C, Mendell J R, Miller J P, Moxley III R T, Park J H, Provine M A, Florence J, Kaiser K K. Clinical investigation in Duchenne muscular dystrophy: penicillamine and vitamin E.  Muscle Nerve. 1988;  11 1164-1168
• 32 Griggs R C, Moxley III R T, Mendell J R, Fenichel G M, Brooke M H, Pestronk A, Miller J P, Cwik V A, Pandya S, Robison J. Duchenne dystrophy: randomized, controlled trial of prednisone (18 months) and azathioprine (12 months).  Neurology. 1993;  3 Pt 1 520-527
• 33 Sharma K R, Mynhier M A, Miller R G. Cyclosporine increases muscular force generation in Duchenne muscular dystrophy.  Neurology. 1993;  3 Pt 1 527-532
• 34 Griggs R C, Pandya S, Florence J M, Brooke M H, Kingston W, Miller J P, Chutkow J, Herr B E, Moxley III R T. Randomized controlled trial of testosterone in myotonic dystrophy.  Neurology. 1989;  2 Pt 1 219-222
• 35 Sugino M, Ohsawa N, Ito T, Ishida S, Yamasaki H, Kimura F, Shinoda K. A pilot study of dehydroepiandrosterone sulfate in myotonic dystrophy.  Neurology. 1998;  2 586-589
• 36 Fenichel G M, Griggs R C, Kissel J, Kramer T I, Mendell J R, Moxley III R T, Pestronk A, Sheng K, Florence J, King W M, Pandya S, Robison V D, Wang H. A randomized efficacy and safety trial of oxandrolone in the treatment of Duchenne dystrophy.  Neurology. 2001;  8 1075-1079
• 37 Fenichel G, Pestronk A, Florence J, Robison V, Hemelt V. A beneficial effect of oxandrolone in the treatment of Duchenne muscular dystrophy: a pilot study.  Neurology. 1997;  5 1225-1226
• 38 Vlachopapadopoulou E, Zachwieja J J, Gertner J M, Manzione D, Bier D M, Matthews D E, Slonim A. E. Metabolic and clinical response to recombinant human insulin-like growth factor I in myotonic dystrophy - a clinical research center study.  J Clin Endocrinol Metab. 1995;  12 3715-3723
• 39 Cittadini A, Ines Comi L, Longobardi S, Rocco Petretta V, Casaburi C, Passamano L, Merola B, Durante-Mangoni E, Sacca L, Politano L. A preliminary randomized study of growth hormone administration in Becker and Duchenne muscular dystrophies.  Eur Heart J. 2003;  7 664-672
• 40 Wagner K R, Hamed S, Hadley D W, Gropman A L, Burstein A H, Escolar D M, Hoffman E P, Fischbeck K H. Gentamicin treatment of Duchenne and Becker muscular dystrophy due to nonsense mutations.  Ann Neurol. 2001;  6 706-711
• 41 Kissel J T, McDermott M P, Mendell J R, King W M, Pandya S, Griggs R C, Tawil R. Randomized, double-blind, placebo-controlled trial of albuterol in facioscapulohumeral dystrophy.  Neurology. 2001;  8 1434-1440
• 42 Kissel J T, McDermott M P, Natarajan R, Mendell J R, Pandya S, King W M, Griggs R C, Tawil R. Pilot trial of albuterol in facioscapulohumeral muscular dystrophy. FSH-DY Group.  Neurology. 1998;  5 1402-1406
• 43 Moxley III R T, Brooke M H, Fenichel G M, Mendell J R, Griggs R C, Miller J P, Province M A, Patterson V. Clinical investigation in Duchenne dystrophy. VI. Double-blind controlled trial of nifedipine.  Muscle Nerve. 1987;  1 22-33
• 44 Mendell J R, Griggs R C, Moxley III R T, Fenichel G M, Brooke M H, Miller J P, Province M A, Dodson W E. Clinical investigation in Duchenne muscular dystrophy: IV. Double-blind controlled trial of leucine.  Muscle Nerve. 1984;  7 535-541
• 45 Toifl K, Presterl E, Graninger W. [Ineffectiveness of diltiazem in Duchenne muscular dystrophy: a placebo-controlled double-blind study].  Wien Klin Wochenschr. 1991;  8 232-235
• 46 Pernice W, Beckmann R, Ketelsen U P, Frey M, Schmidt-Redemann B, Haap K P, Roehren R, Sauer M. A double-blind placebo controlled trial of diltiazem in Duchenne dystrophy.  Klin Wochenschr. 1988;  13 565-570
• 47 Bertorini T E, Palmieri G M, Griffin J, Igarashi M, Hinton A, Karas J G. Effect of dantrolene in Duchenne muscular dystrophy.  Muscle Nerve. 1991;  6 503-507
• 48 Heckmatt J, Rodillo E, Dubowitz V. Management of children: pharmacological and physical.  Br Med Bull. 1989;  3 788-801
• 49 Dubowitz V, Heckmatt J. Management of muscular dystrophy. Pharmacological and physical aspects.  Br Med Bull. 1980;  2 139-144
• 50 Finsterer J, Stollberger C. The heart in human dystrophinopathies.  Cardiology. 2003;  1 1-19
• 51 Finsterer J, Stollberger C, Blazek G, Spahits E. Cardiac involvement in myotonic dystrophy, Becker muscular dystrophy and mitochondrial myopathy: a five-year follow-up.  Can J Cardiol. 2001;  10 1061-1069
• 52 Ruiz-Cano M J, Delgado J F, Jimenez C, Jimenez S, Cea-Calvo L, Sanchez V, Escribano P, Gomez M A, Gil-Fraguas L, Saenz de la Calzada C. Successful heart transplantation in patients with inherited myopathies associated with end-stage cardiomyopathy.  Transplant Proc. 2003;  4 1513-1515
• 53 Rees W, Schuler S, Hummel M, Hetzer R. Heart transplantation in patients with muscular dystrophy associated with end-stage cardiomyopathy.  J Heart Lung Transplant. 1993;  5 804-807
• 54 Stollberger C, Finsterer J, Keller H, Mamoli B, Slany J. Progression of cardiac involvement in patients with myotonic dystrophy, Becker's muscular dystrophy and mitochondrial myopathy during a 2-year follow-up.  Cardiology. 1998;  3 173-179
• 55 Goertzen M, Baltzer A, Voit T. Clinical results of early orthopaedic management in Duchenne muscular dystrophy.  Neuropediatrics. 1995;  5 257-259
• 56 Forst R, Forst J. Importance of lower limb surgery in Duchenne muscular dystrophy.  Arch Orthop Trauma Surg. 1995;  2 106-111
• 57 Bach J R, McKeon J. Orthopedic surgery and rehabilitation for the prolongation of brace-free ambulation of patients with Duchenne muscular dystrophy.  Am J Phys Med Rehabil. 1991;  6 323-331
• 58 Do T. Orthopedic management of the muscular dystrophies.  Curr Opin Pediatr. 2002;  1 50-53
• 59 Forst R, Forst J, Heller K D, Hengstler K. [Characteristics in the treatment of scoliosis in muscular diseases].  Z Orthop Ihre Grenzgeb. 1997;  2 95-105
• 60 Shapiro F, Sethna N, Colan S, Wohl M E, Specht L. Spinal fusion in Duchenne muscular dystrophy: a multidisciplinary approach.  Muscle Nerve. 1992;  5 604-614
• 61 Galasko C S, Delaney C, Morris P. Spinal stabilisation in Duchenne muscular dystrophy.  J Bone Joint Surg Br. 1992;  2 210-214
• 62 Robinson D, Galasko C S, Delaney C, Williamson J B, Barrie J L. Scoliosis and lung function in spinal muscular atrophy.  Eur Spine J. 1995;  5 268-273
• 63 Bach J R, Campagnolo D I, Hoeman S. Life satisfaction of individuals with Duchenne muscular dystrophy using long-term mechanical ventilatory support.  Am J Phys Med Rehabil. 1991;  3 129-135
• 64 Eagle M, Baudouin S V, Chandler C, Giddings D R, Bullock R, Bushby K. Survival in Duchenne muscular dystrophy: improvements in life expectancy since 1967 and the impact of home nocturnal ventilation.  Neuromuscul Disord. 2002;  10 926-929
• 65 Annane D, Chevrolet J C, Chevret S, Raphael J C. Nocturnal mechanical ventilation for chronic hypoventilation in patients with neuromuscular and chest wall disorders.  Cochrane Database Syst Rev. 2000;  2 CD001941
• 66 Brahams D. Postoperative monitoring in patients with muscular dystrophy.  Lancet. 1989;  8670 1053-1054
• 67 Ririe D G, Shapiro F, Sethna N F. The response of patients with Duchenne's muscular dystrophy to neuromuscular blockade with vecuronium.  Anesthesiology. 1998;  2 351-354
• 68 Bennun M, Goldstein B, Finkelstein Y, Jedeikin R. Continuous propofol anaesthesia for patients with myotonic dystrophy.  Br J Anaesth. 2000;  3 407-409
• 69 Richards W C. Anaesthesia and serum creatine phosphokinase levels in patients with Duchenne's pseudohypertrophic muscular dystrophy.  Anaesth Intensive Care. 1972;  2 150-153
• 70 Rosenbaum H K, Miller J D. Malignant hyperthermia and myotonic disorders.  Anesthesiol Clin North America. 2002;  3 385-426
• 71 Breucking E, Reimnitz P, Schara U, Mortier W. [Anesthetic complications. The incidence of severe anesthetic complications in patients and families with progressive muscular dystrophy of the Duchenne and Becker types].  Anaesthesist. 2000;  3 187-195
• 72 Wang J M, Stanley T H. Duchenne muscular dystrophy and malignant hyperthermia - two case reports.  Can Anaesth Soc J. 1986;  4 492-497
• 73 Chalkiadis G A, Branch K G. Cardiac arrest after isoflurane anaesthesia in a patient with Duchenne's muscular dystrophy.  Anaesthesia. 1990;  1 22-25
• 74 Dickey R P, Ziter F A, Smith R A. Emery-Dreifuss muscular dystrophy.  J Pediatr. 1984;  4 555-559
• 75 Gasser T, Dichgans M, Jurkat-Rott K, Klockgether T, Klopstock T, Kretzschmar H, Lehmann-Horn F, Reichmann H, Rolfs A, Sander T, Stogbauer F. [Molecular diagnosis of hereditary neurologic diseases. Position paper].  Nervenarzt. 2000;  10 774-796
• 76 Tawil R, McDermott M P, Pandya S, King W, Kissel J, Mendell J R, Griggs R C. A pilot trial of prednisone in facioscapulohumeral muscular dystrophy. FSH-DY Group.  Neurology. 1997;  1 46-49
• 77 Angelini C, Fanin M, Menegazzo E, Freda M P, Duggan D J, Hoffman E P. Homozygous alpha-sarcoglycan mutation in two siblings: one asymptomatic and one steroid-responsive mild limb-girdle muscular dystrophy patient.  Muscle Nerve. 1998;  6 769-775
• 78 Johnsen S D. Prednisone therapy in Becker's muscular dystrophy.  J Child Neurol. 2001;  11 870-871
• 79 Walter M C, Reilich P, Lochmuller H, Kohnen R, Schlotter B, Hautmann H, Dunkl E, Pongratz D, Muller-Felber W. Creatine monohydrate in myotonic dystrophy: a double-blind, placebo-controlled clinical study.  J Neurol. 2002;  12 1717-1722