Zusammenfassung
Die neurologischen System-Manifestationen der HIV-Infektion haben sich nach Einführung
der antiretroviralen Therapie 1996 nicht wie die extranervalen Komplikationen zurückgebildet,
sondern nehmen in den letzten Jahren - wie internationale Studien ausweisen - relativ
gesehen - wieder zu. Der klinisch und in der ambulanten Versorgung tätige Arzt sollte
daher diese Krankheitsbilder - auch in ihren Frühstadien - erkennen können. Der vorliegende
Artikel beschreibt Symptome sowie bildgebungs- und liquortechnische Diagnostik und
die Therapie primär HIV-1-assoziierter Erkrankungen wie der Enzephalo- und Myelopathie
und der Polyneuropathien. Ferner werden diejenigen opportunistischen Erkrankungen,
Infektionen durch Bakterien, Viren und Parasiten, die bei manifester Immunschwäche
auftreten und heutzutage noch von zahlenmäßiger Relevanz sind, nach diagnostischen,
differenzialdiagnostischen und therapeutischen Gesichtspunkten dargestellt. Ein gesonderter
Abschnitt ist der hochaktiven, antiretroviralen Therapie (HAART) und ihren Interaktionen
mit neurologisch/psychiatrischen Standardtherapien gewidmet.
Abstract
After the introduction of highly active antiretroviral therapy (HAART) in 1996 the
neurological manifestations of human immunodeficiency virus (HIV-1)-infection did
not decline in incidence and prevalence like the other complications of immunodeficiency;
in contrast, due to the longer survival times of HAART treated HIV-1-positive individuals,
prevalence of virus associated neurological disease increased during the last years,
as international studies underline. Therefore, clinicians and HIV-therapists should
be able to diagnose HIV-1-associated neurological disease even in early stages. This
article describes symptoms and signs, neuro-imaging and cerebrospinal fluid findings
as well as therapy options in primary HIV-1-associated neurological disease like encephalo-
and myelopathy and polyneuropathy. Furthermore, those opportunistic infections, caused
by bacteria, viruses other than HIV and parasites emerging with manifest immunodeficiency
and remaining to be relevant in the HAART era are presented from diagnostic, differential-diagnostic
and therapeutic points of view. An extra paragraph describes the interaction of HAART
with neurological/psychiatric standard therapies.
Literatur
- 1
Dore G J, Correll P K, Li Y, Kaldor J M, Cooper D A, Brew BJ.
Changes to AIDS dementia complex in the era of highly active antiretroviral therapy.
Aids.
1999;
13
1249-1253
- 2
Dore G J, McDonald A, Li Y, Kaldor J M, Brew B J,. National HIV Surveillance Committee
.
Marked improvement in survival following AIDS dementia complex in the era of highly
active antiretroviral therapy.
AIDS.
2003;
17
1539-1545
- 3
Eggers C.
HIV-1 associated encephalopathy and myelopathy.
J Neurol.
2002;
249
1132-1136
- 4
Arendt G, Hefter H, Elsing C, Neuen J E, Strohmeyer G, Freund H J.
Neue elektrophysiologische Befunde zur Häufigkeit der Gehirnbeteiligung bei klinisch-neurologisch
asymptomatischen HIV-Infizierten (New electrophysiological findings on the incidence
of brain involvement in clinically and neurologically asymptomatic HIV infections).
Zeitschrift für Elektroenzephalographie, Elektromyographie und verwandte Gebiete.
1989;
20
280-287
- 5
Arendt G, Hefter H, Elsing C, Strohmeyer G, Freund H J.
Motor dysfunction in HIV-infected patients without clinically detectable central-nervous
deficit.
Journal of Neurology.
1990;
237
362-368
- 6
Arendt G, Hefter H, Hilperath F, Giesen H J von, Strohmeyer G, Freund H J.
Motor analysis predicts progression in HIV-associated brain disease.
Journal of the Neurological Sciences.
1994;
123
180-185
- 7 Arendt G. Die Bedeutung quantifizierender elektrophysiologischer Parameter für die
Erfassung der Verlaufskinetik HIV assoziierter zerebraler Erkrankungen. 1994
- 8
Schmitt F A, Bigley J W, McKinnis R, Logue P E, Evans R W, Drucker J L.
Neuropsychological outcome of zidovudine (AZT) treatment of patients with AIDS and
AIDS-related complex.
N Engl J Med.
1988;
319
1573-1578
- 9
Arendt G, Hefter H, Buescher L, Hilperath F, Elsing C, Freund H J.
Improvement of motor performance of HIV-positive patients under AZT therapy.
Neurology.
1992;
42
891-896
- 10
Janssen R S, Cornblath D R, Epstein L G, Foa R P, McArthur J C, Price R W, Asbury A K,
Beckett A, Benson D F, Bridge T P, Leventhal C M, Satz P, Saykin A J, Sidtis J J,
Tross S.
Nomenclature and research case definitions for neurologic manifestations of human
immunodeficiency virus-type 1 (HIV-1) infection.
Neurology.
1991;
41
778-785
- 11
Berger J R, Arendt G.
HIV dementia: the role of the basal ganglia and dopaminergic systems.
J Psychopharmacol.
2000;
14
214-221
- 12
Berger J R, Nath A.
HIV dementia and the basal ganglia.
Intervirology.
1997;
40
122-131
- 13
Chuang H T, Devins G M, Hunsley J, Gill J M.
Psychosocial Distress and Well-Being Among Gay and Bisexual Men With Human Immunodeficiency
Virus Infection.
American Journal of Psychiatry.
1989;
146
876-880
- 14
Neuen-Jacob E, Arendt G, Wendtland B, Jacob B, Schneeweis M, Wechsler W.
Frequency and topographical distribution of CD68-positive macrophages and HIV-1 core
proteins in HIV-associated brain lesions.
Clin Neuropathol.
1993;
12
315-324
- 15
Wenserski F, Giesen H J von, Wittsack H J, Aulich A, Arendt G.
Human Immunodeficiency Virus 1-associated Minor Motor Disorders: Perfusion-weighted
MR Imaging and H MR Spectroscopy.
Neuroradiology.
2003;
228
185-192
- 16
Chang L, Ernst T, Leonido-Yee M, Witt M, Speck O, Walot I, Miller E N.
Highly active antiretroviral therapy reverses brain metabolite abnormalities in mild
HIV dementia.
Neurology.
1999;
53
782-789
- 17
Giesen H J von, Antke C, Hefter H, Wenserski F, Seitz R J, Arendt G.
Potential time course of human immunodeficiency virus type 1-associated minor motor
deficits: electrophysiologic and positron emission tomography findings.
Arch Neurol.
2000;
57
1601-1607
- 18
Ellis R J, Hsia K, Spector S A, Nelson J A, Heaton R K, Wallace M R, Abramson I, Atkinson J H,
Grant I, McCutchan J A.
Cerebrospinal fluid human immunodeficiency virus type 1 RNA levels are elevated in
neurocognitively impaired individuals with acquired immunodeficiency syndrome. HIV
Neurobehavioral Research Center Group.
Ann Neurol.
1997;
42
679-688
- 19
Ellis R J.
HIV dynamics in cerebrospinal fluid (CSF) after antiretroviral therapy initiation
and interruption.
J Neurovirol.
2002;
8 (suppl 1)
1-51
- 20
Gisslen M, Hagberg L, Fuchs D, Norkrans G, Svennerholm B.
Cerebrospinal fluid viral load in HIV-1-infected patients without antiretroviral treatment:
a longitudinal study.
J Acquir Immune Defic Syndr Hum Retrovirol.
1998;
17
291-295
- 21
Gisslen M, Fuchs D, Svennerholm B, Hagberg L.
Cerebrospinal fluid viral load intrathecal immunoactivation and cerebrospinal fluid
monocytic cell count in HIV-1 infection.
J Acquir Immune Defic Syndr.
1999;
21
271-276
- 22
Lipton S A, Yeh M, Dreyer E B.
Update on current models of HIV-related neuronal injury: platelet-activating factor,
arachidonic acid and nitric oxide.
Adv Neuroimmunol.
1994;
4
181-188
- 23
Lipton S A.
Similarity of neuronal cell injury and death in AIDS dementia and focal cerebral ischemia:
potential treatment with NMDA open-channel blockers and nitric oxide-related species.
Brain Pathol.
1996;
6
507-517
- 24
Kaul M, Garden G A, Lipton S A.
Pathways to neuronal injury and apoptosis in HIV-associated dementia.
Nature.
2001;
410
988-994
- 25
Lipton S A.
HIV-associated neural injury and apoptosis: excitotoxins chemokines and caspases.
J Neurovirol.
2002;
8 (suppl 1)
41
- 26
Köller H, Schaal H, Giesen H J von, Arendt G.
TNF-a and gp 120 induced astroglial dysfunction - implications for HIV-1 associated
encephalopathy.
J Neurovirol.
2002;
8 (suppl 1)
41
- 27
Köller H, Schaal H, Rosenbaum C, Giesen H J von, Müller H W, Arendt G.
CXCR4 receptor mediated HIV-1 gp120-induced intracellular calcium dysregulation in
cultured rat cortical astrocytes.
J Neurovirol.
2002;
8 (suppl 1)
9
- 28
Mayne M, Bratanich A C, Chen P, Rana F, Nath A, Power C.
HIV-1 tat molecular diversity and induction of TNF-alpha: implications for HIV-induced
neurological disease.
Neuroimmunomodulation.
1998;
5
184-192
- 29
Nath A.
Pathobiology of human immunodeficiency virus dementia.
Semin Neurol.
1999;
19
113-127
- 30
Toborek M, Pu H, Flora G, Lee Y W, Hennig B, Nath A.
The HIV protein Tat-induced induction of inflammatory responses in the brain tissue.
J Neurovirol.
2002;
8 (suppl 1)
43
- 31
Giesen H J von, Köller H, Theisen A, Arendt G.
Therapeutic Effects of Nonnucleoside Reverse Transcriptase Inhibitors on the Central
Nervous System in HIV-1-Infected Patients.
J Acquir Immune Defic Syndr.
2002;
29
363-367
- 32
Arendt G, Giesen H J von, Hefter H, Theisen A.
Therapeutic effects of nucleoside analogues on psychomotor slowing in HIV infection.
AIDS.
2001;
15
493-500
- 33
Portegies P.
HIV-1, the brain and combination therapy.
The Lancet.
1995;
346
1244-1245
- 34
Tyor W R, Wesselingh S L, Griffin J W, McArthur J C, Griffin D E.
Unifying hypothesis for the pathogenesis of HIV-associated dementia complex, vacuolar
myelopathy and sensory neuropathy.
J Acquir Immune Defic Syndr Hum Retrovirol.
1995;
9
379-388
- 35
Simpson D M, Wolfe D E.
Neuromuscular complications of HIV infection and its treatment.
AIDS.
1991;
5
917-926
- 36
McArthur J C, Yiannoutsos C, Simpson D M, Adornato B T, Singer E J, Hollander H, Marra C,
Rubin M, Cohen B A, Tucker T, Navia B A, Schifitto G, Katzenstein D, Rask C, Zaborski L,
Smith M E, Shriver S, Millar L, Clifford D B.
A phase II trial of nerve growth factor for sensory neuropathy associated with HIV
infection. AIDS Clinical Trials Group Team 291 [In Process Citation].
Neurology.
2000;
54
1080-1088
- 37
Berger J R, Simpson D M.
The pathogenesis of diffuse infiltrative lymphocytosis syndrome: an AIDS-related peripheral
neuropathy [editorial; comment].
Neurology.
1998;
50
855-857
- 38
Moulignier A, Authier F J, Baudrimont M, Pialoux G, Belec L, Polivka M, Clair B, Gray F,
Mikol J, Gherardi R K.
Peripheral neuropathy in Human Immunodeficiency Virus-infected patients with the diffuse
infiltrative lymphocytosis syndrome.
Annals of Neurology.
1997;
41
438-445
- 39
Gherardi R K, Chretien F, Delfau-Larue M H, Authier F J, Moulignier A, Roulland-Dussoix D,
Belec L.
Neuropathy in diffuse infiltrative lymphocytosis syndrome: an HIV neuropathy, not
a lymphoma [see comments].
Neurology.
1998;
50
1041-1044
- 40
Anders H J, Goebel F D.
Neurological manifestations of cytomegalovirus infection in the acquired immunodeficiency
syndrome.
Int J STD AIDS.
1999;
10
151-159
quiz 160-161
- 41
Simpson D M, Tagliati M.
Nucleoside Analogue-Associated Peripheral Neuropathy in Human Immunodeficiency Virus
Infection.
Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology.
1995;
9
153-161
- 42
Simpson D.
Peripheral neuropathies associated with HIV and antiretroviral therapies.
J Neurovirol.
2002;
8 (suppl 1)
3
- 43
Berger A R, Arezzo J C, Schaumburg H H, Skowron G, Merigan T, Bozette S, Richman D,
Soo W.
2,3′-Dideoxycytidine (ddC) toxic neuropathy.
Neurology.
1993;
43
358-362
- 44 Arendt G, Giesen H-J von. Klinik, Pathogenese und Therapie von Neuro-AIDS. Bremen,
London, Boston: Uni-Med Verlag AG 2000
- 45
Giesen H J von, Hefter H, Jablonowski H, Arendt G.
Stavudine (2,3′-Didehydro-3′deoxythymidine; D4T) and the peripheral nerve in HIV-1-infected
patients.
Journal of Neurology.
1999;
246
211-217
- 46
Dalakas M C, Pezeshkpour G H.
Neuromuscular diseases associated with Human Immunodeficiency Virus infection.
Ann Neurol.
1988;
23 (Suppl)
S38-S48
- 47
Dalakas M C, Illa I, Pezeshkpour G H, Laukaitis J P, Cohen B, Griffin J L.
Mitochondrial myopathy caused by long-term zidovudine therapy [see comments].
N Engl J Med.
1990;
322
1098-1105
- 48
Cupler E J, Leon-Monzon M, Miller J, Semino-Mora C, Anderson T L, Dalakas M C.
Inclusion body myositis in HIV-1 and HTLV-1 infected patients.
Brain.
1996;
119
1887-1893
- 49
Gertner E, Thurn J R, Williams D N, Simpson M, Balfour Jr H H, Rhame F, Henry K.
Zidovudine-associated myopathy.
Am J Med.
1989;
86
814-818
- 50
Simpson D M, Slasor P, Dafni U, Berger J, Fischl M A, Hall C.
Analysis of myopathy in a placebo-controlled zidovudine trial.
Muscle Nerve.
1997;
20
382-385
- 51
Pezeshkpour G, Illa I, Dalakas M C.
Ultrastructural characteristics and DNA immunocytochemistry in human immunodeficiency
virus and zidovudine-associated myopathies.
Hum Pathol.
1991;
22
1281-1288
- 52
DNAA .
Aktuelle Diagnostik und Therapie opportunistischer Hirnerkrankungen bei AIDS.
Dtsch Med Wochenschr.
2002;
127
1479-1485
- 53
Bossi P, Caumes E, Astagneau P, Li T S, Paris L, Mengual X, Katlama C, Bricaire F.
[Epidemiologic characteristics of cerebral toxoplasmosis in 399 HIV-infected patients
followed between 1983 and 1994].
Rev Med Interne.
1998;
19
313-317
- 54
Giudici B, Vaz B, Bossolasco S, Casari S, Brambilla A M, Luke W, Lazzarin A, Weber T,
Cinque P.
Highly active antiretroviral therapy and progressive multifocal leukoencephalopathy:
effects on cerebrospinal fluid markers of JC virus replication and immune response
[In Process Citation].
Clin Infect Dis.
2000;
30
95-99
- 55
Weber T, Turner R W, Frye S, Luke W, Kretzschmar H A, Luer W, Hunsmann G.
Progressive multifocal leukoencephalopathy diagnosed by amplification of JC virus-specific
DNA from cerebrospinal fluid.
Aids.
1994;
8
49-57
- 56
Giesen H J von, Neuen-Jacob E, Dörries K, Jablonowski H, Roick H, Arendt G.
Diagnostic criteria and clinical procedures in HIV-1-associated progressive multifocal
leukoencephalopathy.
Journal of Neurological Sciences.
1997;
147
63-72
- 57
Arendt G. DNAA f. d. D.N.A.A .
Antiretrovirale Therapie - Strategien aus Sicht des Neurologen.
Deutsches Ärzteblatt.
2000;
97
B-831-B-832
Prof. Dr. Gabriele Arendt
Neurologische Klinik des Universitätsklinikums Düsseldorf (UKD)
Moorenstr 5
40225 Düsseldorf
Email: Gabriele.Arendt@uni-duesseldorf.de
