Abstract
Objective
To find out whether HIV-associated subclinical psychomotor slowing is present in HIV-infected
children despite effective highly active antiretroviral therapy (HAART).
Patients and Methods
An electrophysiological motor test battery shown to sensitively describe HIV-associated
CNS disease in adults (tremor peak frequency []TPF], most rapid alternating movements
[MRAM], reaction time [RT] and contraction time [CT]) was performed in 17 HIV seropositive
(+) right-handed children. Results were compared to 16 HIV seronegative (-) children.
Results
HIV (-) children showed slower frequencies (TPF, MRAM) and longer RT and CT than (-)
adults. They showed a significant correlation (p = 0.0263) between RT (right = dominant
hand) and age. HIV (+) children showed significant prolongations of RT (right hand)
and CT (both hands) compared to HIV (-) children. RT right hand did not accelerate
with age in HIV (+) children. CT were significantly prolonged in 10 children with
detectable HIV plasma viral burden and normal in 7 children with no detectable HIV
plasma viral load. There was no correlation between CT and CD 4 cell counts.
Conclusions
Despite effective HAART, electrophysiological motor testing in HIV (+) children reveals
significant subclinical CNS dysfunction, especially in children with insufficient
viral load suppression.
Key words
HIV - children - encephalopathy - psychomotor slowing - central nervous system
References
- 1
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
- 2
Arendt G, Hefter H, Elsing C, Strohmeyer G, Freund H J.
Motor dysfunction in HIV-infected patients without clinically detectable central-nervous
deficit.
J Neurol.
1990;
237
362-368
- 3
Arendt G, Hefter H, Hilperath F, von Giesen H J, Strohmeyer G, Freund H J.
Motor analysis predicts progression in HIV-associated brain disease.
J Neurol Sci.
1994;
123
180-185
- 4
Aylward E H, Henderer J D, McArthur J C. et al .
Reduced basal ganglia volume in HIV-1-associated dementia: Results from quantitative
neuroimaging.
Neurology.
1993;
43
2099-2104
- 5
Belman A L, Diamond G, Dickson D. et al .
Pediatric acquired immunodeficiency syndrome. Neurologic syndromes.
Am J Dis Child.
1988;
142
29-35
- 6
Belman A L, Lantos G, Horoupian D. et al .
AIDS: calcification of the basal ganglia in infants and children.
Neurology.
1986;
36
1192-1199
- 7
Berger J R, Arendt G.
HIV dementia: the role of the basal ganglia and dopaminergic systems.
J Psychopharmacol.
2000;
14
214-221
- 8
Berger J R, Nath A.
HIV dementia and the basal ganglia.
Intervirology.
1997;
40
122-131
- 9
Blanche S, Tardieu M, Duliege A. et al .
Longitudinal study of 94 symptomatic infants with perinatally acquired human immunodeficiency
virus infection. Evidence for a bimodal expression of clinical and biological symptoms.
Am J Dis Child.
1990;
144
1210-1215
- 10
Blanchette N, Smith M L, Fernandes-Penney A, King S, Read S.
Cognitive and motor development in children with vertically transmitted HIV infection.
Brain Cogn.
2001;
46
50-53
- 11
Cooper E R, Hanson C, Diaz C. et al .
Encephalopathy and progression of human immunodeficiency virus disease in a cohort
of children with perinatally acquired human immunodeficiency virus infection. Women
and Infants Transmission Study Group.
J Pediatr.
1998;
132
808-812
- 12
de Martino M, Tovo P A, Balducci M. et al .
Reduction in mortality with availability of antiretroviral therapy for children with
perinatal HIV-1 infection. Italian Register for HIV Infection in Children and the
Italian National AIDS Registry.
JAMA.
2000;
284
190-197
- 13
Dickson D W, Llena J F, Nelson S J, Weidenheim K M.
Central nervous system pathology in pediatric AIDS.
Ann N Y Acad Sci.
1993;
693
93-106
- 14
Epstein L G, Sharer L R, Joshi V V, Fojas M M, Koenigsberger M R, Oleske J M.
Progressive encephalopathy in children with Acquired Immune Deficiency Syndrome.
Ann Neurol.
1985;
17
488-496
- 15
Epstein L G, Sharer L R, Oleske J M. et al .
Neurologic manifestations of human immunodeficiency virus infection in children.
Pediatrics.
1986;
78
678-687
- 16
Fowler M G.
Pediatric HIV infection: neurologic and neuro-psychologic findings.
Acta Paediatr.
1994;
400 (Suppl)
59-62
- 17
Gavin P, Yogev R.
Central nervous system abnormalities in pediatric human immunodeficiency virus infection.
Pediatr Neurosurg.
1999;
31
115-123
- 18
Gortmaker S L, Hughes M, Cervia J. et al .
Effect of combination therapy including protease inhibitors on mortality among children
and adolescents infected with HIV-1.
N Engl J Med.
2001;
345
1522-1528
- 19
Janssen R S, Cornblath D R, Epstein L G. et al .
Nomenclature and research case definitions for neurologic manifestations of human
immunodeficiency virus-type 1 (HIV-1) infection.
Neurology.
1991;
41
778-785
- 20
McCoig C, Castrejon M M, Castano E. et al .
Effect of combination antiretroviral therapy on cerebrospinal fluid HIV RNA, HIV resistance,
and clinical manifestations of encephalopathy.
J Pediatr.
2002;
141
36-44
- 21
Mintz M, Epstein L G.
Neurologic manifestations of pediatric acquired immunodeficiency syndrome: clinical
features and therapeutic approaches.
Semin Neurol.
1992;
12
51-56
- 22
Mintz M, Tardieu M, Hoyt L. et al .
Levodopa therapy improves motor function in HIV-infected children with extrapyramidal
syndromes.
Neurology.
1996;
47
1583-1585
- 23
Palella Jr F J, Delaney K M, Moorman A C. et al .
Declining morbidity and mortality among patients with advanced human immunodeficiency
virus infection.
N Engl J Med.
1998;
338
853-860
- 24
Parks R A, Danoff J V.
Motor performance changes in children testing positive for HIV over 2 years.
Am J Occup Ther.
1999;
53
524-528
- 25
Price R W, Yiannoutsos C T, Clifford D B. et al .
Neurological outcomes in late HIV infection: adverse impact of neurological impairment
on survival and protective effect of antiviral therapy. AIDS Clinical Trial Group
and Neurological AIDS Research Consortium study team.
AIDS.
1999;
13
1677-1685
- 26
Raskino C, Pearson D A, Baker C J. et al .
Neurologic, neurocognitive, and brain growth outcomes in human immunodeficiency virus-infected
children receiving different nucleoside antiretroviral regimens. Pediatric AIDS Clinical
Trials Group 152 Study Team.
Pediatrics.
1999;
104
e32
- 27
Sacktor N C, Bacellar H, Hoover D R. et al .
Psychomotor slowing in HIV infection: a predictor of dementia, AIDS, and death.
J Neurovirol.
1996;
2
404-410
- 28
Sacktor N C, Lyles R H, Skolasky R L. et al .
Combination antiretroviral therapy improves psychomotor speed performance in HIV-seropositive
homosexual men. Multicenter AIDS Cohort Study (MACS).
Neurology.
1999;
52
1640-1647
- 29
Sei S, Stewart S K, Farley M. et al .
Evaluation of human immunodeficiency virus (HIV) type 1 RNA levels in cerebrospinal
fluid and viral resistance to zidovudine in children with HIV encephalopathy.
J Infect Dis.
1996;
174
1200-1206
- 30
Spector S A, Hsia K, Pratt D. et al .
Virologic markers of human immunodeficiency virus type 1 in cerebrospinal fluid. The
HIV Neurobehavioral Research Center Group.
J Infect Dis.
1993;
168
68-74
- 31
Stern Y, McDermott M P, Albert S. et al .
Factors associated with incident human immunodeficiency virus-dementia.
Arch Neurol.
2001;
58
473-479
- 32
Tardieu M, Le Chenadec J, Persoz A, Meyer L, Blanche S, Mayaux M J.
HIV-1-related encephalopathy in infants compared with children and adults. French
Pediatric HIV Infection Study and the SEROCO Group.
Neurology.
2000;
54
1089-1095
- 33
Tardieu M, Mayaux M J, Seibel N. et al .
Cognitive assessment of school-age children infected with maternally transmitted human
immunodeficiency virus type 1.
J Pediatr.
1995;
126
375-379
- 34
Tozzi V, Balestra P, Galgani S. et al .
Positive and sustained effects of highly active antiretroviral therapy on HIV-1-associated
neurocognitive impairment.
AIDS.
1999;
13
1889-1897
- 35
Tozzi V, Balestra P, Galgani S. et al .
Changes in neurocognitive performance in a cohort of patients treated with haart for
3 years.
J Acquir Immune Defic Syndr.
2001;
28
19-27
- 36
von Giesen H J, Hefter H, Jablonowski H, Arendt G.
HAART is neuroprophylactic in HIV-1 infection.
J Acquir Immune Defic Syndr.
2000;
23
380-385
- 37
von Giesen H J, Hefter H, Roick H, Mauss S, Arendt G.
HIV-specific changes in the motor performance of HIV-positive intravenous drug abusers.
J Neurol.
1994;
242
20-25
- 38
von Giesen H J, Koller 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
- 39
von Giesen H J, Wittsack H J, Wenserski F, Köller H, Hefter H, Arendt G.
Basal ganglia metabolite abnormalities in HIV-1 associated minor motor deficits.
Arch Neurol.
2001;
58
1281-1286
PD Dr. med. Hans-Jürgen von Giesen
Department of Neurology, Heinrich Heine University of Düsseldorf
Postfach 101007
40001 Düsseldorf
Germany
Email: giesenhj@uni-duesseldorf.de