Neuromyelitis Optica Spectrum Disorders

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Classification according to ICD-10
G36.0 Neuromyelitis optica (Devic's disease)
demyelination in neuritis nervi optici
ICD-10 online (WHO version 2019)

The neuromyelitis optica-spectrum disorders (abbreviated NMOSD of English. Neuromyelitis optica spectrum disorders ) are a group of rare autoimmune- induced inflammatory diseases of the central nervous system . They can typically affect the optic nerve, spinal cord, or brain stem. The classic combination of inflammation of the optic nerve and spinal cord was called neuromyelitis optica ( NMO for short , also Devic syndrome ). This syndrome has meanwhile been reflected in the term neuromyelitis optica spectrum diseases.

root cause

In most cases, it is a matter of autoantibodies (AK) against the v. Virus in the central nervous system . a. protein aquaporin-4 (AQP4) expressed in astrocytes caused autoimmune disease . Some of the AQP4-IgG-negative patients have AK against the so-called myelin oligodendrocyte glycoprotein (MOG-AK). In addition to the antibodies, autoreactive inflammatory cells are also involved in the development of tissue damage .

Typical symptoms and course

  • Visual disturbances up to blindness (amaurosis) of one eye or both eyes within hours to days
  • Incomplete or complete paraplegic syndrome with partly ascending symptoms (e.g. sensory disturbances, weakness / paralysis of the extremities, bladder / rectal disorders, autonomic disorders, pain, tonic spasms, etc.)
  • Insatiable nausea, insatiable vomiting (sometimes misdiagnosed as bulimia ), insatiable hiccups in foci of inflammation in the area postrema of the brain stem
  • Symptomatic narcolepsy (rare) with inflammation foci in the diencephalon
  • Symptomatic brain lesions (e.g. epilepsy ) , especially in children
  • Respiratory paralysis due to inflammation in the brain stem or high cervical spinal cord

The disease is usually relapsing; Monophasic courses have been described, but are very rare in AQP4-IgG-positive patients. The severity of the symptoms varies greatly from one individual to another (i.e. between patients) and intra-individually (i.e. from flare to flare) and ranges from very mild sensory disturbances to complete paraplegic syndromes when the spinal cord is involved and from slightly blurred to complete when the optic nerve is involved - or bilateral loss of vision.

The symptoms present in the flare-up can recede completely or incompletely spontaneously or as a result of a flare-up treatment (see below). If the symptoms present in the episode do not or only partially regress, a disability (limited vision, limited mobility, etc.) can result. Chronic disability progression between relapses, as occurs in patients with multiple sclerosis , is extremely rarely observed in patients with NMO. Preventing the occurrence of new relapses through long-term immunosuppressive treatment (see below) and prompt treatment of relapses is therefore of crucial importance for avoiding and minimizing permanent disability.

Diagnosis

A reliable differentiation from multiple sclerosis is not always possible on the basis of the clinical picture alone, especially at the beginning of the disease. To secure the diagnosis , u. a. the determination of AQP4-AK and MOG-AK as well as a magnetic resonance tomography of the skull and spinal cord, a CSF puncture and the determination of the evoked potentials are recommended. In 2015, new international consensus criteria were published that replaced the 2006 criteria. The new diagnostic criteria make it possible for the first time to make the diagnosis in AQP4-IgG-positive patients who (so far) have only developed one of the two index syndromes (optic neuritis and myelitis) or who have atypically manifested the disease; The authors proposed separate criteria for the AQP4-IgG-negative NMO. The earlier diagnosis made possible by the new diagnostic criteria enables an earlier start of therapy. NMO and its incomplete forms are summarized by the authors as “Neuromyelitis optica spectrum diseases”.

Antibody testing

To test for the presence of AQP4-Ab and MOG-IgG, so-called cell-based assays (CBA) are recommended, which use human full-length protein (AQP4 or MOG) as the target antigen . Other test methods (e.g. ELISA , RIPA ) have proven to be either insufficiently sensitive or insufficiently specific . The test is usually carried out using blood serum; an additional examination of the cerebrospinal fluid is only necessary in special cases. It should be noted that the concentration of the antibodies in the serum (as well as in the CSF ) is subject to considerable fluctuations depending on the disease activity and therapy and, especially under immunosuppressive therapy, can temporarily fall below the detection limit; it is highest in the acute episode of the disease. For this reason and since the detection of AQP4-IgG or MOG-IgG is of therapeutic and prognostic importance, in AK-negative cases a new test should be carried out at a later point in time (also several times).

histology

Histologically , AQP4-IgG-positive NMOs can be found in the foci of inflammation and a. AK and complement deposits , inflammatory cell infiltrates , astrocyte death and , as a secondary phenomenon, d. H. as a result of the death of astrocytes, also a loss of neurons and demyelination (demyelination) of the nerves. However, spinal cord biopsies can result in severe and permanent neurological deficits and are usually not required to confirm the diagnosis; it is recommended before each differential diagnosis contemplated biopsy (. eg differentiating it from tumors of the spinal cord) in patients with suspected NMO necessarily antibodies against AQP4 IgG and antibodies to MOG IgG to determine.

treatment

Treatment is carried out in an episode with high-dose, usually intravenously administered methylprednisolone or, especially if there is no response, which is more common than in multiple sclerosis, by means of plasmapheresis (or - although there are fewer data on effectiveness - by means of immunoadsorption ) . In contrast to multiple sclerosis, which is often treated with immunomodulators , long-term treatment consists primarily of immunosuppression , e.g. with rituximab or azathioprine. It should be noted that some drugs approved for the treatment of MS (e.g. interferon-beta , natalizumab) , possibly also glatiramer acetate , fingolimod and alemtuzumab ) often cannot prevent new NMO attacks or even promote the occurrence of new NMO attacks. A reliable distinction between classic MS and NMO is therefore crucial for treatment and prognosis.

Epidemiology

The disease is rare (about 1–10 per 100,000 inhabitants in western countries). Women are affected significantly more often than men (AQP4-IgG-positive NMO: approx. 9 times more often, MOG-IgG-positive NMO: approx. 3 times more often). The maximum age is around 39 years; however, the disease can in principle appear for the first time at any age.

Nosological classification

The AQP4-AK-positive NMO and the MOG-AK-positive NMO are no longer regarded as special forms of multiple sclerosis (MS), but as separate diseases that can be differentiated in terms of pathogenesis , histopathology , prognosis and therapy .

history

The earliest known reports of patients with possible NMO date from the late 18th and early 19th centuries. In 1844 the Genoese doctor Giovanni Battista Pescetto reported on a 42-year-old man who had developed acute bilateral blindness and acute inflammation of the spinal cord at the same time; Both symptoms resolved completely after excessive bloodletting .

The current term was first used in French in 1894 as neuro-myélite optique aiguë . Eugène Devic used it in a paper presented at the French medical congress in Lyon, as did his student Fernand Gault in the same year as the title of his doctoral thesis. It can therefore not be said with certainty which of the two ultimately invented the term, but there are strong indications in Gault's doctoral thesis that it was Devic. The disease is also known as Devic's syndrome after its name . However, both authors used other names to describe this disease. It was first mentioned in English literature in 1903 in the British Medical Journal at the time as acute optic neuromyelitis and in the German literature in a review by Erwin Stransky . He spoke for the first time of the term neuromyelitis optica, which is widespread today .

Since then, the nosological classification of optic neuromyelitis has changed several times. While Devic and Gault assumed a disease of their own, other authors, e.g. B. Russell Brain, not enough differences between MS and NMO to classify the latter as a separate disease entity. The diagnostic criteria have also been revised several times over the years.

Study group

The Neuromyelitis Optica Study Group (NEMOS) links clinical and scientific activities on neuromyelitis optica for doctors and patients in order to obtain important information on the epidemiology, clinical course, pathogenesis, prognosis and treatment of the disease. NEMOS also publishes recommendations for diagnosis and therapy of NMO.

literature

Web links

Individual evidence

  1. ↑ Urban and Vogel: NMO from now on only as a spectrum disease . In: InFo Neurology & Psychiatry . tape 17 , no. 30 . Springer, 2015, ISSN  1437-062X , p. 30 , doi : 10.1007 / s15005-015-1448-z ( springer.com [accessed April 11, 2019]).
  2. ^ Corinna Trebst: Neuromyelitis optica spectrum diseases . Clinic and Therapy. In: drug therapy . tape 36 , no. 8 . Wissenschaftliche Verlagsgesellschaft Stuttgart, 2018, ISSN  0723-6913 , ZDB -ID 380334-X , p. 237 ( aerztekammer-bw.de [PDF; accessed on April 11, 2019]).
  3. ↑ Todd A. Hardy, Stephen W. Reddel, Michael H. Barnett, Jacqueline Palace, Claudia F. Lucchinetti and Brian G. Weinshenke: Atypical inflammatory demyelinating syndromes of the CNS . In: Lancet Neurology . tape 15 , no. 9 , August 2016, p. 967 , doi : 10.1016 / S1474-4422 (16) 30043-6 , PMID 27478954 (English, thelancet.com [accessed April 11, 2019]).
  4. ↑ a b c d e S. Jarius, K. Ruprecht, B. Wildemann, T. Kuempfel, M. Ringelstein, C. Geis, I. Kleiter, Christoph Kleinschnitz, A. Berthele, J. Brettschneider, K. Hellwig, B Hemmer, R. Linker, F. Lauda, ​​CA Mayer, H. Tumani, A. Melms, C. Trebst, M. Stangel, M. Marziniak, F. Hoffmann, S. Schippling, J. Faiss, O. Neuhaus, B. Ettrich, C. Zentner, K. Guthke, U. Hofstadt-van Oy, R. Reuss, H. Pellkofer, U. Ziemann, P. Kern, KP Wandinger, F. Then Bergh, T. Boettcher, S. Langel , M. Liebetrau, PS Rommer, S. Niehaus, C. Münch, A. Winkelmann, U. Zettl, I. Metz, C. Veauthier, JP Sieb, C. Wilke, HP Hartung, O. Aktas, F. Paul: Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients. In: Journal of neuroinflammation. Volume 9, January 2012, p. 14, doi: 10.1186 / 1742-2094-9-14 . PMID 22260418 , PMC 3283476 (free full text).
  5. ^ S. Jarius, B. Wildemann. AQP4 antibodies in neuromyelitis optica: diagnostic and pathogenetic relevance. In: Nat Rev Neurol. 6 (7), 2010, pp. 383-392.
  6. ↑ MC Papadopoulos, AS Verkman: Aquaporin 4 and neuromyelitis optica. In: The Lancet Neurology . 11, 2012, pp. 535-544, doi: 10.1016 / S1474-4422 (12) 70133-3 .
  7. ↑ S. Mader, V. Gredler, K. Schanda, K. Rostasy, I. Dujmovic, K. Pfaller, A. Lutterotti, S. Jarius, F. Di Pauli, B. Kuenz, R. Ehling, H. Hegen, F. Deisenhammer, F. Aboul-Enein, MK Storch, P. Koson, J. Drulovic, W. Kristoferitsch, T. Berger, M. Reindl: Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders. In: Journal of neuroinflammation. Volume 8, December 2011, p. 184, doi: 10.1186 / 1742-2094-8-184 . PMID 22204662 , PMC 3278385 (free full text).
  8. ↑ a b S. Jarius, B. Wildemann, F. Paul: Neuromyelitis optica: clinical features, immunopathogenesis and treatment. In: Clin Exp Immunol. 176 (2), 2014, pp. 149-164.
  9. ↑ a b M. Levy, B. Wildemann, S. Jarius, B. Orellano, S. Sasidharan, MS Weber, O. Stuve: Immunopathogenesis of neuromyelitis optica. In: Advances in immunology. Volume 121, 2014, pp. 213-242, doi: 10.1016 / B978-0-12-800100-4.00006-4 . PMID 24388217 (Review).
  10. ↑ a b c d e f g h i C. Trebst, S. Jarius, A. Berthele, F. Paul, S. Schippling, B. Wildemann, N. Borisow, I. Kleiter, O. Aktas, T Kümpfel; Neuromyelitis Optica Study Group (NEMOS): Update on the diagnosis and treatment of neuromyelitis optica: recommendations of the Neuromyelitis Optica Study Group (NEMOS). In: Journal of neurology. Volume 261, No. 1, January 2014, pp. 1–16, doi: 10.1007 / s00415-013-7169-7 . PMID 24272588 , PMC 3895189 (free full text) (review).
  11. ↑ a b DM Wingerchuk, B. Banwell, JL Bennett, P. Cabre, W. Carroll, T. Chitnis, J. de Seze, K. Fujihara, B. Greenberg, A. Jacob, S. Jarius, M. Lana- Peixoto, M. Levy, JH Simon, S. Tenembaum, AL Traboulsee, P. Waters, KE Wellik, BG Weinshenker; International Panel for NMO Diagnosis: International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. In: Neurology. Volume 85, No. 2, July 2015, pp. 177-189, doi: 10.1212 / WNL.0000000000001729 . PMID 26092914 , PMC 4515040 (free full text).
  12. ↑ a b c d e S. Jarius, B. Wildemann: Aquaporin-4 antibodies (NMO-IgG) as a serological marker of neuromyelitis optica: a critical review of the literature. In: Brain Pathol. 23 (6), Nov 2013, pp. 661-683. PMID 24118483 (free full text).
  13. ^ S. Jarius, D. Franciotta, F. Paul, K. Ruprecht, R. Bergamaschi, PS Rommer, R. Reuss, C. Probst, W. Kristoferitsch, KP Wandinger, B. Wildemann: Cerebrospinal fluid antibodies to aquaporin-4 in neuromyelitis optica and related disorders: frequency, origin, and diagnostic relevance. In: Journal of neuroinflammation. Volume 7, September 2010, p. 52, doi: 10.1186 / 1742-2094-7-52 . PMID 20825655 , PMC 2945323 (free full text).
  14. ↑ M. Ringelstein, I. Metz, K. Ruprecht, A. Koch, J. Rappold, J. Ingwersen, C. Mathys, S. Jarius, W. Brück, HP Hartung, F. Paul, O. Aktas; Neuromyelitis Optica Study Group (NEMOS): Contribution of spinal cord biopsy to diagnosis of aquaporin-4 antibody positive neuromyelitis optica spectrum disorder. In: Mult Scler. 20 (7), 2014, pp. 882-888.
  15. ^ I. Kleiter, A. Gahlen, N. Borisow, K. Fischer, KD Wernecke, B. Wegner, K. Hellwig, F. Pache, K. Ruprecht, J. Havla, M. Krumbholz, T. Kümpfel, O. Aktas, HP Hartung, M. Ringelstein, C. Geis, C. Kleinschnitz, A. Berthele, B. Hemmer, K. Angstwurm, JP Stellmann, S. Schuster, M. Stangel, F. Lauda, ​​H. Tumani, C. Mayer, L. Zeltner, U. Ziemann, R. Linker, M. Schwab, M. Marziniak, F. Then Bergh, U. Hofstadt-van Oy, O. Neuhaus, A. Winkelmann, W. Marouf, J. Faiss, B. Wildemann, F. Paul, S. Jarius, C. Trebst; Neuromyelitis Optica Study Group: Neuromyelitis Optica : Evaluation of 871 attacks and 1,153 treatment courses. In: Ann Neurol. Volume 79, No. 2, 2016, pp. 206-216.
  16. ↑ M. Krumbholz, U. Hofstadt-van Oy, K. Angstwurm, I. Kleiter, S. Jarius, F. Paul, O. Aktas, G. Buchholz, P. Kern, A. Straube, T. Kümpfel: Very late -onset neuromyelitis optica spectrum disorder beyond the age of 75. In: Journal of Neurology. Volume 262, No. 5, 2015, pp. 1379-1384.
  17. ↑ a b c d e Sven Jarius and Brigitte Wildemann: The history of neuromyelitis optica . In: Journal of Neuroinflammation . tape 10 , no. 8 , 2013, ISSN  1742-2094 , doi : 10.1186 / 1742-2094-10-8 , PMID 23320783 , PMC 3599417 (free full text).
  18. ^ S. Jarius, B. Wildemann: The history of neuromyelitis optica. Part 2: 'Spinal amaurosis', or how it all began . In: Journal of Neuroinflammation . 16, No. 1, November 2018, p. 280. doi : 10.1186 / s12974-019-1594-1 . PMID 31883522 . PMC 6935230 (free full text).
  19. ↑ S. Jarius, B. Wildemann: 'Noteomielite' accompanied by acute amaurosis (1844). An early case of neuromyelitis optica . In: Journal of the Neurological Sciences . 313, No. 1-2, February 2015, pp. 182-184. doi : 10.1016 / j.jns.2011.09.025 . PMID 21992815 .
  20. ↑ E. Devic: Myélite aiguë dorsal-lombaire avec nevrite optique. Autopsy. In Congrès français de médecine (Premiere Session; Lyon, 1894; procès-verbaux, mémoires et discussions; publiés par M. le Dr L. Bard). Paris: Lyon: Asselin et Houzeau, Louis Savy; 1895, pp. 434-439.
  21. ^ F. Gault: De la neuromyélite optique aiguë. Faculté de Médecine et de Pharmacie, Thése 1894.