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Fortschr Neurol Psychiatr 2003; 71(8): 406-414
DOI: 10.1055/s-2003-41193
Originalarbeit
© Georg Thieme Verlag Stuttgart · New York

Neurologische Komplikationen entzündlicher intestinaler Erkrankungen: Zöliakie, Morbus Whipple, Morbus Crohn und Colitis ulcerosa

Neurological Complications of Inflammatory Intestinal DiseasesW.  Dietrich1 , F.  Erbguth1
  • 1Klinik für Neurologie, Klinikum Nürnberg (Süd) (Leiter: Prof. Dr. med. Dipl.-Psych. F. Erbguth)
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Publication History

Publication Date:
11 August 2003 (online)

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Abstract

A number of neurological symptoms have been described as complications of inflammatory bowel disorders such as coeliac disease, Whipple's disease, Crohn's disease and ulcerative colitis. The neurology of coeliac disease includes disorders of the central nervous system encompassing cerebellar ataxia, epilepsy, myoclonus, dementia and multifocal leukoencephalopathy. Peripheral neuropathies, of axonal and demyelinating types, and myopathies have also been reported. The pathomechanisms are more related to immunological-inflammatory processes than to a malresorptive vitamin deficiencies. While CNS symptoms of coeliac disease show a poor response to gluten restriction, peripheral symptoms may respond to elimination of gluten from the diet. There are few reports of a successful corticosteroid treatment in patients showing inflammatory findings in the CSF or bioptic material. Whipple's disease is caused by the gram-positive bacillus Tropheryma whipplei. Patients with a central nervous system manifestation of Whipple's disease may develop a variety of symptoms including dementia, supranuclear gaze palsy, movement disorders, hypothalamic dysfunction and myorhythmia. The CNS-infection is diagnosed by PCR of the CSF. Long-term antibiotic treatment is required, and relapses may occur after withdrawal of antimicrobial therapy. Crohn's disease and ulcerative colitis are complicated by various forms of polyneuropathies, and arterial and venous cerebrovascular diseases. In most cases with neurological complications of inflammatory gastrointestinal diseases an immune mediated inflammatory process is suspected to be the underlying pathomechanism.

Zusammenfassung

Die entzündlichen Darmerkrankungen Zöliakie, Morbus Whipple, Morbus Crohn und Colitis ulcerosa können mit einer Reihe neurologischer Komplikationen einhergehen. Bei der Zöliakie sind Manifestationen am Zentralnervensystem in Form von zerebellärer Ataxie, Epilepsie, Myoklonien, Demenzen und multifokalen Leukenzephalopathien beschrieben. Auch können axonale oder demyelinisierende Polyneuropathien oder selten Myopathien auftreten. Pathogenetisch verantwortlich sind vor allem immunologisch-inflammatorische Mechanismen und nur selten malresorptiv bedingte Vitamindefizite. Während die ZNS-Symptome in der Regel kaum auf eine glutenfreie Kost ansprechen, ist dies bei den peripheren Manifestationen meist der Fall. Daneben sind in Einzelfällen erfolgreiche Kortikosteroidgaben bei bioptisch gesicherter entzündlicher Manifestation beschrieben. Der durch den Erreger Tropheryma whipplei verursachte Morbus Whipple kann im Rahmen einer zerebralen Beteiligung mit Gedächtnis- und Bewusstseinsstörungen, supranukleärer Blickparese, Bewegungsstörungen, hypothalamischen Störungen und Myorhythmien einhergehen. Die Erkrankung lässt sich durch eine PCR im Liquor diagnostizieren und erfordert eine lange antibiotische Therapie, bei deren Absetzen es nicht selten zu Rückfällen kommt. Zu den neurologischen Komplikationen des M. Crohn und der Colitis ulcerosa gehören unterschiedliche Formen von Polyneuropathien sowie arterielle und venöse zerebrovaskuläre Manifestationen. In den meisten Fällen werden die neurologischen Komplikationen entzündlicher Darmerkrankungen durch immunvermittelte Entzündungsprozesse verursacht.

Literatur

  • 1 Schultz M, Hellerbrand C. Viele Fälle bleiben unbekannt.  Deutsches Ärzteblatt. 2002;  28 - 29 1949-1950
    PubMedGoogle Scholar
  • 2 Kieslich M, Errazuriz G, Posselt H G, Moeller-Hartmann W, Zanella F, Boehles H. Brain white-matter lesions in celiac disease: a prospective study of 75 diet-treated patients.  Pediatrics. 2001;  108 E21-E21
    CrossrefPubMedGoogle Scholar
  • 3 Wills A J. The neurology and neuropathology of coeliac disease.  Neuropathol Appl Neurobiol. 2000;  26 493-496
    CrossrefPubMedGoogle Scholar
  • 4 Hadjivassiliou M, Gibson A, Davies-Jones G A, Lobo A J, Stephenson T J, Milford-Ward A. Does cryptic gluten sensitivity play a part in neurological illness?.  Lancet. 1996;  347 369-371
    CrossrefPubMedGoogle Scholar
  • 5 Hadjivassiliou M, Chattopadhyay A K, Davies-Jones G AB, Gibson A, Grünewald R A, Lobo A J. Neuromuscular disorder as a presenting feature of coeliac disease.  J Neurol Neurosurg Psychiatry. 1997;  63 770-775
    PubMedGoogle Scholar
  • 6 Luostarinen L, Pirttila T, Collin P. Coeliac disease presenting with neurological disorders.  Eur Neurol. 1999;  42 132-135
    CrossrefPubMedGoogle Scholar
  • 7 Gobbi G, Bouquet F, Greco L, Lambertini A, Tassinari C A, Ventura A, Zaniboni M G. Coeliac disease, epilepsy and cerebral calcifications.  Lancet. 1992;  340 439-443
    CrossrefPubMedGoogle Scholar
  • 8 Mantia L la, Pollo B, Savoiardo M, Costa A, Eoli M, Allegranza A, Boiardi A, Cestari C. Meningo-cortical calcifying angiomatosis and celiac disease.  Clin Neurol Neurosurg. 1998;  100 209-215
    CrossrefPubMedGoogle Scholar
  • 9 Magaudda A, Bernardina B dalla, Marco P de, Sfaello Z, Longo M, Colamaria V, Daniele O, Tortorella G, Tata M A, Perri R di, Meduri M. Bilateral occipital calcification, epilepsy and coeliac disease: clinical and neuroimaging features of a new syndrome.  J Neurol Neurosurg Psychiatry. 1993;  56 885-889
    PubMedGoogle Scholar
  • 10 Mumford C J, Fletcher N A, Ironside J W, Warlow C P. Progressive ataxia, focal seizures and malabsorption syndrome in a 41 year old woman.  J Neurol Neurosurg Psychiatry. 1996;  60 225-230
    PubMedGoogle Scholar
  • 11 Beyenburg S, Scheid B, Deckert-Schlüter M, Lagreze H. Chronic progressive leukoencephalopathy in adult celiac disease.  Neurology. 1998;  50 820-822
    PubMedGoogle Scholar
  • 12 Kepes J J, Chou S M, Price L W. Progressive multifocal leukoencephalopathy with 10-year survival in a patient with nontropical sprue. Report of a case with unusual light and electron microscopic features.  Neurology. 1975;  25 1006-1012
    PubMedGoogle Scholar
  • 13 Hadjivassiliou M, Grünewald R A, Davies-Jones G AB. Gluten sensitivity as a neurological illness.  J Neurol Neurosurg Psychiatry. 2002;  72 560-563
    CrossrefPubMedGoogle Scholar
  • 14 Collin P, Pirttila T, Nurmikko T, Somer H, Erila T, Keyrilainen O. Celiac disease, brain atrophy and dementia.  Neurology. 1991;  41 372-375
    PubMedGoogle Scholar
  • 15 Özge A, Karakelle A, Kaleagasi H. Celiac disease associated with recurrent stroke: a coincidence or cerebral vasculitis?.  Eur J Neurol. 2001;  8 373-374
    CrossrefPubMedGoogle Scholar
  • 16 Brücke T, Kollegger H, Schmidbauer M, Müller C, Podreka I, Deecke L. Adult coeliac disease and brainstem encephalitis.  J Neurol Neurosurg Psychiatry. 1988;  51 456-457
    PubMedGoogle Scholar
  • 17 Ghezzi A, Filippi M, Falini A, Zaffaroni M. Cerebral involvement in celiac disease: a serial MRI study in a patient with brainstem and cerebellar symptoms.  Neurology. 1997;  49 1447-1450
    PubMedGoogle Scholar
  • 18 Hadjivassiliou M, Grunewald R A, Chattopadhyay A K, Davies-Jones G A, Gibson A, Jarratt J A, Kandler R H, Lobo A, Powell T, Smith C ML. Clinical, radiological, neurophysiological and neuropathological characteristics of gluten ataxia.  Lancet. 1998;  352 1582-1585
    CrossrefPubMedGoogle Scholar
  • 19 Hadjivassiliou M, Grunewald R A, Davies-Jones G AB. Idiopathic cerebellar ataxia associated with celiac disease: lack of distinctive neurological features.  J Neurol Neurosurg Psychiatry. 1999;  67 257
    PubMedGoogle Scholar
  • 20 Hadjivassiliou M, Grunewald R A, Davies-Jones A, Simpson J, Woodroofe N, Smith C. Gluten ataxia: insights into the pathophysiology.  J Neurol Neurosurg Psychiatry. 1999;  67 262
    PubMedGoogle Scholar
  • 21 Bürk K, Bösch S, Müller C A, Melms A, Zühlke C, Stern M, Besenthal I, Skalej M, Ruck P, Ferber S, Klockgether T, Dichgans J. Sporadic cerebellar ataxia associated with gluten sensitivity.  Brain. 2001;  124 1013-1019
    CrossrefPubMedGoogle Scholar
  • 22 Pellecchia M T, Scala R, Filla A, Michele G de, Ciacci C, Barone P. Idiopathic cerebellar ataxia associated with celiac disease: lack of distinctive neurological features.  J Neurol Neurosurg Psychiatry. 1999;  66 32-35
    CrossrefPubMedGoogle Scholar
  • 23 Bushara K O, Goebel S U, Shill H, Goldfarb L G, Hallett M. Gluten sensitivity in sporadic and hereditary cerebellar ataxia.  Ann Neurol. 2001;  49 540-543
    CrossrefPubMedGoogle Scholar
  • 24 Abele M, Bürk K, Schols L, Schwartz S, Besenthal I, Dichgans J, Zuhlke C, Riess O, Klockgether T. The aetiology of sporadic adult-onset ataxia.  Brain. 2002;  125 961-968
    CrossrefPubMedGoogle Scholar
  • 25 Kaplan J G, Pack D, Horoupian D, DeSouza T, Brin M, Schaumburg H. Distal axonopathy associated with chronic gluten enteropathy: a treatable disorder.  Neurology. 1988;  38 642-645
    CrossrefPubMedGoogle Scholar
  • 26 Perkin G D, Murray-Lyon I. Neurology and the gastrointestinal system.  J Neurol Neurosurg Psychiatry. 1998;  65 291-300
    PubMedGoogle Scholar
  • 27 Jensen K, Sollid L M, Scott H. Gliadin-specific T cell responses in peripheral blood of healthy individuals involve T cell clones restricted by the coeliac disease associated DQ heterodimer.  Scand J Immunol. 1995;  42 166-170
    CrossrefPubMedGoogle Scholar
  • 28 Hadjivassiliou M, Boscolo S, Davies-Jones G AB, Grünewald R A, Not T, Sanders D S, Simpson J E, Tongiorgi E, Williamson C A, Woodroofe N M. The humoral response in the pathogenesis of gluten ataxia.  Neurology. 2002;  58 1221-1226
    PubMedGoogle Scholar
  • 29 Shan L, Molberg O, Parrot I, Hausch F, Filiz F, Gray G M, Sollid L M, Khosla C. Structural basis for gluten intolerance in celiac sprue.  Science. 2002;  297 2275-2279
    CrossrefPubMedGoogle Scholar
  • 30 Schuppan D, Hahn E G. Gluten and the gut - Lessons for Immune regulation.  Science. 2002;  297 2218-2220
    CrossrefPubMedGoogle Scholar
  • 31 Trier J S. Celiac sprue.  N Eng J Med. 1991;  325 1709-1718
    PubMedGoogle Scholar
  • 32 Hadjivassiliou M, Grunewald R A, Lawden M, Davies-Jones G AB, Powell T, Smith C ML. Headache and CNS white matter abnormalities associated with gluten sensitivity.  Neurology. 2001;  56 385-388
    PubMedGoogle Scholar
  • 33 Pellecchia M T, Scala R, Perretti A, DeMichele G, Santoro L, Filla A, Ciacci C, Barone P. Cerebellar ataxia associated with subclinical celiac disease responding to gluten-free diet.  Neurology. 1999;  53 1606-1608
    PubMedGoogle Scholar
  • 34 Anderson M. Neurology of Whipple's disease.  J Neurol Neurosurg Psychiatry. 2000;  68 2-5
    PubMedGoogle Scholar
  • 35 Durand D V, Lecomte C, Cathebras P, Rousset H, Godeau P. Whipple disease. Clinical review of 52 cases.  Medicine. 1997;  76 170-184
    CrossrefPubMedGoogle Scholar
  • 36 Knox D L, Green W R, Troncoso J C, Yardley J H, Hsu J, Zee D S. Cerebral ocular Whipple's disease: A 62-year odyssey from death to diagnosis.  Neurology. 1995;  45 617-625
    PubMedGoogle Scholar
  • 37 Louis E D, Lynch T, Kaufmann P, Fahn S, Odel J. Diagnostic guidelines in central nervous system Whipple's disease.  Ann Neurol. 1996;  40 561-568
    CrossrefPubMedGoogle Scholar
  • 38 Simpson D A, Wishnow R, Gargulinski R B, Pawlak A M. Oculo-facial myorhythmia in central nervous system Whipple's disease: a additional case and review of the literature.  Mov Disord. 1995;  10 195-200
    CrossrefPubMedGoogle Scholar
  • 39 Töpper R, Gartung C, Block F. Neurologische Komplikationen bei entzündlichen Darmerkrankungen.  Nervenarzt. 2002;  73 489-500
    CrossrefPubMedGoogle Scholar
  • 40 Herbay A, Ditton H J, Schuhmacher F. Whipple's disease: staging and monitoring by cytology and polymerase chain reaction analysis of cerebrospinal fluid.  Gastroenterology. 1997;  113 434-441
    CrossrefPubMedGoogle Scholar
  • 41 Manzel K, Tranel D, Cooper G. Cognitive and behavioral abnormalities in a case of central nervous system Whipple disease.  Arch Neurol. 2000;  57 399-403
    CrossrefPubMedGoogle Scholar
  • 42 Schwartz M A, Selhorst J B, Ochs A L, Beck R W, Campbell W W, Harris J K, Waters B, Velasco M E. Oculomasticatory myorhythmia: A unique movement disorder occuring in Whipple's disease.  Ann Neurol. 1986;  20 677-683
    CrossrefPubMedGoogle Scholar
  • 43 Schnider P, Trattnig S, Kolleger H, Auff E. MR of cerebral Whipple disease.  Am J Neuroradiol. 1995;  16 1328-1329
    PubMedGoogle Scholar
  • 44 Kremer S, Besson G, Bonaz B, Pasquier B, Bas J le, Grand S. Diffuse lesions in the CNS revealed by MR imaging in a case of Whipple disease.  Am J Neuroradiol. 2001;  22 493-495
    PubMedGoogle Scholar
  • 45 Wroe S J, Pires M, Harding B, Youl B D, Shorvon S. Whipple's disease confined to the CNS presenting with multiple intracerebral mass lesions.  J Neurol Neurosurg Psychiatry. 1991;  54 989-992
    PubMedGoogle Scholar
  • 46 Keinath R D, Merell D E, Vliestra R. Antibiotic treatment and relapse in Whipple's disease. Long-term follow-up of 88 patients.  Gastroenterology. 1985;  88 1867-1873
    PubMedGoogle Scholar
  • 47 Schnider P J, Reisinger E C, Gerschlager W. Long-term follow-up in cerebral Whipple's disease.  Eur J Gastroenterol Hepatol. 1996;  8 899-903
    PubMedGoogle Scholar
  • 48 Ramzan N N, Loftus E Jr, Burgart L J. Diagnosis and monitoring of Whipple disease by polymerase chain reaction.  Ann Intern Med. 1997;  126 520-527
    PubMedGoogle Scholar
  • 49 Shanahan F. Crohn's disease.  Lancet. 2002;  359 62-69
    CrossrefPubMedGoogle Scholar
  • 50 Greenstein A J, Janowitz H D, Sachar D. The extra-intestinal complications of Crohn's disease and ulcerative colitis: a study of 700 patients.  Medicine. 1976;  55 401-412
    CrossrefPubMedGoogle Scholar
  • 51 Lossos A, River Y, Eliakim A, Steiner I. Neurologic aspects of inflammatory bowel disease.  Neurology. 1995;  45 416-421
    CrossrefPubMedGoogle Scholar
  • 52 Moormann B, Herath H, Mann O, Ferbert A. Beteiligung des peripheren Nervensystems bei Morbus Crohn.  Nervenarzt. 1999;  70 1107-1111
    CrossrefPubMedGoogle Scholar
  • 53 Humbert P, Monnier G, Billerey C, Birgen C, Dupond J L. Polyneuropathy: an unusual extraintestinal manifestation of Crohn's disease.  Acta Neurol Scand. 1989;  80 301-306
    PubMedGoogle Scholar
  • 54 Nemni R, Fazio R, Corbo M, Sessa M, Comi G, Canal N. Peripheral neuropathy associated with Crohn's disease.  Neurology. 1987;  37 1414-1417
    PubMedGoogle Scholar
  • 55 Neundörfer B. Neurologische Begleiterkrankungen des M. Crohn.  Fortschr Neurol Psychiat. 1992;  60 481-486
    PubMedGoogle Scholar
  • 56 Lindgren S, Lilja B, Rosen I, Sundkvist G. Disturbed autonomic nerve function in patients with Crohn's disease.  Scand J Gastroenterol. 1991;  26 361-366
    PubMedGoogle Scholar
  • 57 Druschky A, Heckmann J, Engelhardt A, Neundörfer B. Myositis - eine seltene Komplikation des M. Crohn.  Fortschr Neurol Psychiat. 1996;  64 422-424
    PubMedGoogle Scholar
  • 58 Leibowitz G, Eliakim R, Amir A, Rachmilewitz D. Dermatomyositis associated with Crohn's disease.  J Clin Gastroenterol. 1994;  18 48-52
    PubMedGoogle Scholar
  • 59 Gold R, Kappos L, Becker T. Development of multiple sclerosis in patient on long-term sulfasalazine.  Lancet. 1990;  335 409-410
    PubMedGoogle Scholar
  • 60 Sigsbee B, Rottenberg D A. Sagittal sinus thrombosis as a complication of regional enteritis.  Ann Neurol. 1978;  3 450-452
    CrossrefPubMedGoogle Scholar
  • 61 Schneiderman J H, Sharpe J A, Sutton D MC. Cerebral and retinal vascular complications of inflammatory bowel disease.  Ann Neurol. 1979;  5 331-337
    CrossrefPubMedGoogle Scholar
  • 62 Gobbele R, Reith W, Block F. Zerebrale Vaskulitis als neurologische Begleiterkrankung bei Morbus Crohn.  Nervenarzt. 2000;  71 299-304
    CrossrefPubMedGoogle Scholar
  • 63 Nelson J, Barron M M, Riggs J E, Gutmann L, Schochet SS Jr. Cerebral vasculitis and ulcerative colitis.  Neurology. 1986;  36 719-721
    PubMedGoogle Scholar
  • 64 Druschky A, Heckmann J G, Druschky K, Huk W J, Erbguth F, Neundörfer B. Severe neurological complications of ulcerative colitis.  J Clin Neuroscience. 2002;  9 84-86
    PubMedGoogle Scholar
  • 65 Kraus J A, Nahser H-C, Berlit P. Lymphocytic encephalomyeloneuritis as a neurologic complication of ulcerative colitis.  J Neur Sci. 1996;  141 117-119
    CrossrefPubMedGoogle Scholar
  • 66 Walker J C, Selva D, Pietris G, Crompton J L. Optic disc swelling in Crohn's disease.  Aust NZ J Ophthalmol. 1998;  26 329-332
    PubMedGoogle Scholar
  • 67 Knox D L, Schachat A P, Mustonen E. Primary, secondary and coincidental ocular complications of Crohn's disease.  Ophthalmology. 1984;  91 163-173
    PubMedGoogle Scholar
  • 68 Ernst B B, Lowder C Y, Meisler D M. Posterior segment manifestations of inflammatory bowel disease.  Ophthalmology. 1991;  98 1272-1280
    PubMedGoogle Scholar
  • 69 Duker J S, Brown G C, Brooks L. Retinal vasculitis in Crohn's disease.  Am J Ophthalmol. 1987;  103 664-668
    PubMedGoogle Scholar
  • 70 Ruby A J, Jampol L M. Crohn's disease and retinal vascular disease.  Am J Ophthalmol. 1990;  110 349-353
    PubMedGoogle Scholar
  • 71 Grant T L, Kay M D, Bienfang D C. Pseudotumor cerebri associated with corticosteroid withdrawal in inflammatory bowel disease.  Am J Ophthalmol. 1994;  117 352-357
    PubMedGoogle Scholar

Wenke Dietrich,
Prof. Dr. Frank Erbguth

Klinik für Neurologie · Klinikum Nürnberg Süd

Breslauer Str. 201

90471 Nürnberg

Email: erbguth@klinikum-nuernberg.de

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