Pathophysiologie und Therapie des reversiblen posterioren Leukoenzephalopathiesyndroms (RPLS)

Zusammenfassung

Das posteriore reversible Leukoenzephalopathiesyndrom (RPLS) ist eine neurologische Erkrankung, die zunehmende Aufmerksamkeit in der medizinischen Fachliteratur erfährt. Das zeigt sich deutlich in der Zunahme an Veröffentlichungen in den letzten zwei Jahren. Sie führt zu ödematösen Veränderungen der weißen Substanz besonders im posterioren Parietal- und Okzipitallappen, den Basalganglien und dem Kleinhirn. Die Erkrankung ist häufig durch neurologische Symptome wie Kopfschmerzen, zentrale Sehstörungen, Übelkeit mit Erbrechen, qualitativen und quantitativen Bewusstseinsstörungen, Orientierungsstörungen und Krampfanfällen gekennzeichnet. Das RPLS ist häufig mit einer plötzlichen hypertensiven Entgleisung assoziiert und betrifft meistens Patienten mit Eklampsie, Niereninsuffizienz und hypertensiver Enzephalopathie. Auch die Therapie mit Immunsuppressiva und Immunmodulatoren, wie Zyklosporin A, Tacrolimus, Interferon-α und Filgastrim kann ein RPLS auslösen. Eine besondere Form des RPLS ist die isolierte Leukoenzephalopathie des Hirnstammes, die v. a. durch die Diskordanz ausgeprägter kernspintomographischer Veränderungen und geringen klinischen Symptomen gekennzeichnet ist. Die Läsionen des RPLS lassen sich kernspintomographisch in der FLAIR- und T₂-Gewichtung als diffuse Signalanhebungen der weißen Substanz darstellen. Die Diffusionsgewichtung ist eine wichtige differenzialdiagnostische Hilfe um das überwiegend vasogene Ödem des RPLS vom zytotoxischen Ödem einer akuten Ischämie zu unterscheiden. Die Therapie besteht in einer konsequenten und raschen Einstellung hypertoner Blutdruckwerte. Darunter ist die Symptomatik zumeist reversibel und die MRT-Veränderungen bilden sich zurück. Deshalb ist die schnelle Diagnosestellung beim RPLS besonders wichtig. Bei Verzögerung der richtigen Behandlung kann es zu bleibenden Schäden der betroffenen Hirnregionen kommen. Die vorliegende Übersichtarbeit soll den aktuellen Stand zur Pathophysiologie, Diagnostik und Therapie des RPLS darstellen. Zudem wird besonders auf die isolierte reversible Leukoenzephalopathie des Hirnstammes eingegangen.

Abstract

Reversible posterior leukoencephalopathy syndrome (RPLS) is a widely recognized neurological disorder, considering the increasing number of publications over the past two years. Oedematous cerebral white matter lesions particularly involve the posterior parietal and occipital lobes, but may also affect the brainstem, basal ganglia and cerebellum. This leads to characteristic neurological symptoms such as headache, visual disturbances, nausea and vomiting, altered mental status and seizures. This syndrome is often associated with an abrupt increase in blood pressure, mainly in patients with eclampsia, renal insufficiency and hypertensive encephalopathy. Immunosuppressive and immunomodulating drugs such as cyclosporine A, tacrolimus, interferone-α and filgastim may also lead to RPLS. A rare variant of RPLS is the isolated brainstem leukoencephalopathy, which is characterized by extensive MRI lesions associated with little clinical symptoms. The respective lesions are best visualized with FLAIR and T₂-weighted magnetic resonance imaging. They show diffuse hyperintensity generally involving cerebral parieto-occipital regions, but may also selectively affect the brainstem without accompanying supratentorial lesions. Diffusion weighted imaging is an important diagnostic tool to differentiate the mainly vasogenic edema of RPLS from the cytotoxic edema of acute cerebral ischaemia. Appropriate therapy consists of rapid and sustained correction of hypertension. Symptoms can be completely reversible and MRI lesions may show complete remission. Early recognition of RPLS is extremely important, because of its benign prognosis under therapy. Delay of appropriate treatment, however, may lead to permanent damage of affected brain tissue. This review will give an overview of current knowledge of pathophysiology, diagnostic procedures and treatment options on RPLS. Special consideration will be given to reversible isolated brainstem leukoencephalopathy.

Literatur

• 1 Chattergee S N. Hypertensive encephalopathy.  J Indiana State Med Assoc. 1950;  19 420-421
• 2 Hinchey J, Chaves C, Appignani B. et al . A reversible posterior leukoencephalopathy syndrome.  N Engl J Med. 1996;  334 494-500
• 3 Pavlakis S G, Frank Y, Kalina P. et al . Occipital-parietal encephalopathy: a new name for an old syndrome.  Pediatr Neurol. 1997;  16 145-148
• 4 Pavlakis S G, Frank Y, Chusid R. Hypertensive encephalopathy, reversible occipitoparietal encephalopathy, or reversible posterior leukoencephalopathy: three names for an old syndrome.  J Child Neurol. 1999;  14 277-281
• 5 Leniger T, Kastrup O, Diener H C. Reversible posterior leukoencephalopathy syndrome induced by granulocyte stimulating factor filgastrim.  J Neurol Neurosurg Psychiatry. 2000;  69 280-281
• 6 Sanders T G, Clayman D A, Sanchez-Ramos L. et al . Brain in eclampsia: MR imaging with clinical correlation.  Radiology. 1991;  180 475-478
• 7 Schwartz R B, Jones K M, Kalina P. et al . Hypertensive encephalopathy: findings on CT, MR imaging, and SPECT imaging in 14 cases.  AJR Am J Roentgenol. 1992;  159 379-383
• 8 Klippel N De, Sennesael J, Lamote J. et al . Cyclosporin leukoencephalopathy induced by intravenous lipid solution.  Lancet. 1992;  339 1114
• 9 Casey S O, Truwit C L. Pontine reversible edema: a newly recognized imaging variant of hypertensive encephalopathy?.  AJNR Am J Neuroradiol . 2000;  21 243-245
• 10 Seze J De, Mastain B, Stojkovic T. et al . Unusual MR Findings of the Brain Stem in Arterial Hypertension.  AJNR Am J Neuroradiol. 2000;  21 391-394
• 11 Robertson D M, Dinsdale H B, Ayashi T. et al . Cerebral lesions in adrenal regeneration hypertension.  Am J Pathol. 1970;  59 115-132
• 12 Dinsdale H B, Robertson D M, Chiang T Y. et al . Hypertensive cerebral microinarction and cerebrovascular reactivity.  Eur Neurol. 1971 - 1972;  6 29-33
• 13 Dinsdale H B, Robertson D M, Haas R A. Cerebral blood flow in acute hypertension.  Arch Neurol. 1974;  31 80-87
• 14 Johannson B B. The blood-brain barrier and cerebral blood flow in acute hypertension.  Acta Med Scand. 1983;  678, Suppl 107-112
• 15 Bryom F B. The pathogenesis of hypertensive encephalopathy and its relation to the malignant phase of hypertension: experimental evidence from the hypertensive rat.  Lancet. 1954;  2 201-211
• 16 Gray T S, Morley J E. Neuropeptide Y: anatomical distribution and possible function in mammalian nervous system.  Life Sci. 1986;  38 389-401
• 17 Truwit C L, Denaro C P, Lake J R. et al . MR imaging of reversible cyclosporin A-induced neurotoxicity.  AJNR Am J Neuroradiol. 1991;  12 651-659
• 18 Urushitani M, Seriu N, Udaka F. et al . MRI demonstration of a reversible lesion in cerebral deep white matter in thrombotic thrombocytopenic purpura.  Neuroradiology. 1996;  38 137-138
• 19 Skinhoj E, Standgoard S. Pathogenesis of hypertensive encephalopathy.  Lancet. 1973;  I 461-462
• 20 Delanty N, Vaughan C J. Seizures, hypertension and posterior leukoencephalopathy. In: Delanty N (ed) Seizures: Medical Causes and Management. New Jersey; Human Press 2002: 251-260
• 21 Roberts J M, Redman C WG. Pre-eclampsia: more than pregnancy-induced hypertension.  Lancet. 1993;  342 504
• 22 Donaldson J O. The brain in eclampsia.  Hypertens Pregnancy. 1994;  13 115
• 23 Takano T, Ohno M, Takeuchi Y. et al . Cytotoxic edema and interleukin-6 hypertensive encephalopathy.  Pediatr Neurol . 2002;  26 71-73
• 24 Kastrup O, Maschke M, Wanke I. et al . Posterior reversible encephalopathy syndrome due to severe hypercalcemia.  J Neurol. 2002;  249 1563-1566
• 25 Hughes R L. Cyclosporine-related central nervous system toxicity in cardiac transplantation.  N Engl J Med. 1990;  323 420-421
• 26 Humphreys T R, Leyden J J. Acute reversible central nervous system toxicity associated with low-dose oral cyclosporine therapy.  J Am Acad Dermatol. 1993;  29 490-492
• 27 Groen P C de, Aksamit A J, Rakela J. et al . Central nervous system toxicity after liver transplantation: the role of cyclosporine and cholesterol.  N Engl J Med. 1987;  317 861-866
• 28 Bhatt B D, Meriano F V, Buchwald D. Cyclosporine-associated central nervous system tocicity.  N Engl J Med. 1988;  318 788
• 29 Rubin A M, Kang H. Cerebral blindness and encephalopathy with cyclosporine A toxicity.  Neurology. 1987;  37 1072-1076
• 30 Gottrand F, Largillière C, Farriaux J-P. Cyclosporine neurotoxicity.  N Engl J Med. 1991;  324 1744-1745
• 31 Freise C E, Rowley H, Lake J. et al . Similar clinical presentation of neurotoxicity following FK 506 and cyclosporine in a liver transplant recipient.  Transplatn Proc. 1991;  23 3173-3174
• 32 Igarashi T, Ishigatsubo Y, Ohno S. et al . Central nervous system toxicity related to FK506 in patients with Behçet's disease.  Ann Rheum Dis. 1994;  53 350-351
• 33 Sloane J P, Lwin K Y, Gore M E. et al . Disturbance of blood-brain barrier after bone-marrow transplantation.  Lancet. 1985;  2 280-281
• 34 Eidelmann E H, Abu-Elmagd K, Wilson J. et al . Neurologic complications of FK 506.  Transplant Proc. 1991;  23 3175-3178
• 35 Tollemar J, Ringdén O, Ericzon B-G. et al . Cyclosporine-associated central nervous system toxicity.  N Engl J Med. 1988;  318 788-789
• 36 DeGroen P, Aksamit A, Rakela J. et al . Cyclosporine-associated central nervous system toxicity.  N Engl J Med. 1988;  318 789
• 37 Benigni A, Morigi M, Perico N. et al . The acute effect of FK506 and cyclosporine on endothelial cell function and renal vascular resistance.  Transplantation. 1992;  54 775-780
• 38 Zoja C, Furci L, Ghilardi F. et al . Cyclosporin-induced endothelial cell injury.  Lab Invest. 1986;  55 455-462
• 39 Fogo A, Hakim R C, Sugiura M. et al . Severe endothelial injury in a renal transplant patient receiving cyclosporine.  Transplantation. 1990;  49 1190-1192
• 40 Bunchman T E, Brookshire C A. Cyclosporine-induced synthesis of endothelin by cultured human endothelial cells.  J Clin Invest. 1991;  88 310-314
• 41 Lanzino G, Cloft H, Hemstreet M K. et al . Reversible posterior leukoencephalopathy following organ transplantation: Description of two cases.  Clin Neurol Neurosurg. 1997;  99 222-226
• 42 Haug C, Duell T, Lenich A. et al . Endothelin concentrations in cyclosporin-treated patients after bone marrow transplantation.  Bone Marrow Transplant. 1995;  16 191-194
• 43 Sommer B G, Innes J T, Whitehurst R M. et al . Cyclosporine-associated renal arteriopathy.  Transplant Proc. 1986;  18, Supp 1 151-157
• 44 Sommer B G, Innes J T, Whitehurst R M. et al . Cyclosporine-associated renal arteriopathy resulting in loss of allograft function.  Am J Surg. 1985;  149 756-764
• 45 Brown Z, Neild G H. Cyclosporine inhibits prostacyclin production by cultured human endothelial cells.  Transplant Proc. 1987;  19 1178-1180
• 46 Abu-Elmagd K M, Bronsther O, Kobayashi M. et al . Acute hemolytic enemia in liver and bone marrow transplant patients under FK 506 therapy.  Transplant Proc. 1991;  23 3190-3192
• 47 Perloff D. Hypertension and pregnancy-related hypertension.  Cardiol Clin. 1998;  16 79-101
• 48 Zampaglione B, Pascale C, Marchisio M. et al . Hypertensive urgencies and emergencies. Prevalence and clinical presentation.  Hypertension. 1996;  27 144-147
• 49 Antunes N L, Small T N, George D. et al . Posterior leukoencephalopathy syndrome may not be reversible.  Pediatr Neurol. 1999;  20 241-243
• 50 Chan A K, Bhargava R, Desai S. et al . Reversible posterior leukoencephalopathy syndrome in a child with cerebral X-linked adrenoleukodystrophy treated with cyclosporine after bone marrow transplantation.  J Inherit Metab Dis. 2003;  26 527-536
• 51 Ay H, Buonanno F S, Schaefer P W. et al . Posterior leukoencephalopathy without severe hypertension: utility of diffusion weighted MRI.  Neurology. 1998;  51 1369-1376
• 52 Yoshida K, Yamamoto T, Mori K. et al . Reversible posterior leukoencephalopathy syndrome in a patient with hypertensive encephalopathy - case report. (Tokyo).  Neurol Med Chir . 2001;  41 364-369
• 53 Obeid T, Shami A, Karsou S. The role of seizures in reversible posterior leukoencephalopathy.  Seizure. 2004;  13 277-281
• 54 Bakshi R, Bates V E, Mechtler L L. et al . Occipital lobe seizures as the major clinical manifestation of reversible posterior leukoencephalopathy syndrome: magnetic resonance imaging findings.  Epilepsia. 1998;  39 295-299
• 55 Garg R K. Posterior leukoencephalopathy syndrom.  Postgrad Med J. 2001;  77 24-28
• 56 Wennberg R A. Clinical and MRI evidence that occipital lobe seizures can be the major maninfestation of the reversible posterior leukoencephalopathy syndrome.  Epilepsia. 1998;  39 1381-1383
• 57 Adams H P, Brott T G, Crowell R M. et al . Guidelines for the management of patients with acute ischaemic stroke.  Stroke. 1994;  25 241-243
• 58 Schwartz R B, Mulkern R V, Gudbjartsson H. et al . Diffusion-weighted MR imaging in hypertensive encephalopathy: Clues to pathogenesis.  AJNR Am J Neuroradiol. 1998;  19 859-862
• 59 Schaefer P W, Buonanno F S, Gonzalez R G. et al . Diffusion-weighted imaging discriminates between cytotoxic and vasogenic edema in a patient with eclampsia.  Stroke. 1997;  28 1082-1085
• 60 Thambisetty M, Biousse V, Newman N J. Hypertensive brainstem encephalopathy: clinical and radiographic features.  J Neurol Sci. 2003;  208 93-99
• 61 Morello F, Marino A, Cigolini M. et al . Hypertensive brain stem encephalopathy: clinically silent massive edema of the pons.  Neurol Sci. 2001;  22 317-320
• 62 Kidwell C, Saver J. Thrombolytic reversal of acute human cerebral injury shown by Diffusion/perfusion magnetic resonance imaging.  Ann Neurol. 2002;  47 462-469
• 63 Meyer M A, Galloway G, Khan S. Transient blindness associated with reversible occipital white matter abnormalities: two patients studied by MR, CT, and 18F-FDG PET imaging.  J Neuroimaging. 1998;  8 240-242
• 64 Tajima Y, Isonishi K, Kashiwaba T. et al . Two similar cases of encephalopathy, possibly a reversible posterior leukoencephalopathy syndrome: serial findings of magnetic resonance imaging, SPECT and angiography.  Intern Med. 1999;  38 54-58
• 65 Weidauer S, Gaa J, Sitzer M. et al . Posterior encephalopathy with vasospasm: MRI and angiography.  Neuroradiology. 2003;  45 869-876
• 66 Ito Y, Niwa H, Iida T. et al . Post-transfusion reversible posterior leukoencephalopathy syndrome with cerebral vasoconstriction.  Neurology. 1997;  49 1174-1175
• 67 Henderson R D, Rajah T, Nicol A J. et al . Posterior leukoencephalopathy following intrathecal chemotherapy with MRA-documented vasospasm.  Neurology. 2003;  60 326-328
• 68 Dodick D W, Eross E J, Drazkowski J F. et al . Thunderclap headache associated with reversible vasospasm and posterior leukoencephalopathy syndrome.  Cephalgia. 2003;  23 994-997
• 69 Eichler F S, Wang P, Wityk R J. et al . Diffuse metabolic abnormalities in reversible posterior leukoencephalopathy syndrome.  AJNR Am J Neuroradiol. 2002;  23 833-837
• 70 Schwartz R B. A reversible posterior leukoencephalopathy syndrome (letter).  N Eng J Med. 1996;  334 1743
• 71 Weingarten K, Barbut D, Fillipi C. et al . Acute hypertensive encephalopathy: findings on spin-echo and gradient-echo MR imaging.  Am J Roentgenol. 1994;  162 665-670
• 72 Tuncel M, Ram V C. Hypertensive emergencies: etiology and managment.  Am J Cardiovasc Drugs. 2003;  3 21-31
• 73 Williams O, Brust J C. Hypertensive encephalopathy.  Curr Treat Options Cardiovasc Med. 2004;  6 209-216
• 74 Chang G Y, Keane J R. Hypertensive encephalopathy: three cases presenting with severe brainstem edema.  Neurology. 1999;  53 652-654
• 75 Solinas C, Briellmann R S, Harvey A S. et al . Hypertensive encephalopathy - Antecedent to hippocampal slerosis and temporal lobe epilepsy?.  Neurology. 2003;  60 1534-1536