Neurodevelopmental/ Recovery of child infected w/HIV after retroviral therapy

[Guest guest]

When it's hard to imagine a virus causing the symptoms that have been classified

as developmental, behavioral, psychological, look at AIDS research in children

with similar symptoms:

(This is also a big deal because it shows safety and efficacy of antiretroviral

therapy in kids has already been tested, so there may not be years of delay if

it turns out antiretroviral therapy could be indicated to treat our kids.)

Subject: Neurodevelopmental/ Recovery of child infected w/HIV after retroviral

therapy

 

There are several studies trying to determine whether or not it's beneficial or

warranted to treat young children infected with HIV with antiviral therapy....

 

Note the recovery of symptoms following antiviral therapy!

Also very interesting that the severity of symptoms differs between HIV infected

kids with encephalopathy than those without...

Also note that some of the herpesviruses (and others) are capable of activating

same receptors on brain cells (including neurons) that are know targets of

HIV-1. It would therefore not come as a suprise that more viruses are capable of

exerting the exact same neurological damage, through EXACT same mechanisms as

HIV-1.

Pediatrics. 1998 Mar;101(3):E7.

    Neurodevelopmental/ neuroradiologic recovery of a child infected with HIV

after treatment with combination antiretroviral therapy using the HIV-specific

protease inhibitor ritonavir.

        * Tepper VJ, Department of Pediatrics, University of land School of

Medicine, Baltimore, MD 21201-1585, USA.

    BACKGROUND: Neurodevelopmental impairment has been identified in children

infected with human immunodeficiency virus (HIV). The frequency and spectrum of

neurologic impairment are greater in children than those reported for adults. In

children, HIV is known to enter the central nervous system early in the course

of the disease. The presentation of pediatric neuro-acquired immune deficiency

syndrome ranges from static (eg, nonprogressive developmental delay) to

progressive encephalopathy (eg, acquired microcephaly, pyramidal tract signs,

and spasticity). It has been demonstrated that antiretroviral agents can improve

or even reverse the course of neurologic impairment in children. These changes

have been attributed to various degrees of central nervous system drug

penetration. Increasingly, protease inhibitors and combination antiretroviral

therapy using reverse transcriptase inhibitors are being used in the treatment

of children infected with HIV.

The addition of a protease inhibitor to nucleoside analogue therapy has been

reported to delay disease progression and prolong life in adults with moderate

to advanced HIV disease. No data currently exist on the impact of combination

therapy using two nucleoside analogues and a protease inhibitor on

neurodevelopmental and neurologic function in children with HIV infection. The

following case report presents the effects of combination therapy using

ritonavir in a child infected with HIV. CASE REPORT: An 8-year, 2-month-old

African-American boy was infected with HIV through vertical transmission.

Regular monitoring of the patient's neurodevelopmental status has been conducted

as part of his participation in longitudinal research protocols. For the first

51/2 years of life, his neurodevelopmental status was normal, with cognitive

functioning as measured by standardized psychometric tools solidly in the

average range. Speech and language skills were

age-appropriate. Tests of gross and fine motor functioning as well as evaluation

of overall neurodevelopmental status suggested normal development. Magnetic

resonance imaging (MRI) of the brain was consistently normal. His family

reported that adaptive functioning, peer and family relationships, and behavior

were all within normal limits. School reports indicated consistently that the

patient was performing at age and grade level, with respect to both academic

achievement and behavior. Initial concerns regarding the patient's development

were expressed by both his family and school at age 6 years, 6 months. These

concerns includeddifficulty with classroom work, decreased attention,

word-finding problems, fatigue, staring spells, and loss of strength. His family

and school reported a marked loss of skills acquired previously. Results of

formal psychological and speech and language evaluation reflected statistically

significant drops in test scores from

baseline, with both delayed and atypical skills evident. The patient's condition

worsened rapidly. Within a few months, he was no longer able to use sentences to

communicate. Cognitive testing was attempted, but he was unable to participate

because of significant fatigue, limited attention, and inability to communicate

verbally. His family described periods of disorientation and confusion,

lethargy, and disinterest in age-appropriate activities. He became agitated and

overstimulated easily both in small group settings and in crowds. He

demonstrated both fine and gross motor impairments. When frustrated, he

displayed infantile and autistic-like behavior. MRI with contrast showed diffuse

atrophy as well as mild prominence of the ventricles and sulcii compared with

baseline assessment. In addition to fatigue and neurologic symptoms, wasting

syndrome was diagnosed, with loss of percentiles in both weight and height by

age 71/2 years. Low-grade elevation of

liver function tests and amylase was noted. Blood cultures for mycobacteria were

negative, as were serologic tests for hepatitis. (ABSTRACT TRUN

    PMID: 9493492 [PubMed - indexed for MEDLINE]

full text:

http://pediatrics. aappublications. org/cgi/gca?

allch= & SEARCHID=1 & FULLTEXT=tepper+

hiv & FIRSTINDEX=0 & hits=10 & RESULTFORMAT= & gca=pediatrics% 3B101%2F3%

2Fe7 & gca=pediatrics% 3B118%2F6% 2Fe1745 & gca=pediatrics% 3B102%2F1%

2Fe8 & gca=pediatrics% 3B106%2F2% 2Fe25 & allchb=#101/ 3/e7

PEDIATRICS Vol. 102 No. 1 July 1998, p. e8

ELECTRONIC ARTICLE:

Early Language Development in Children Exposed to or Infected With Human

Immunodeficiency Virus

Received May 28, 1997; accepted Feb 6, 1998.

Coplan, Kathie A. Contello, Coleen K. Cunningham, Leonard B. Weiner,

D. Dye, Roberge, Martha A. Wojtowycz, and Kim Kirkwood

From the Departments of Pediatrics and Obstetrics and Gynecology, State

University of New York, Health Science Center, Syracuse, New York.

Objectives.  To compare language development in infants and young children with

human immunodeficiency virus (HIV) infection to language development in children

who had been exposed to HIV but were uninfected, and (among subjects with HIV

infection) to compare language development with cognitive and neurologic status.

Design.  Prospective evaluation of language development in infected and in

exposed but uninfected infants and young children.

Setting.  Pediatric Infectious Disease Clinic, State University of New

York-Health Science Center at Syracuse.

Subjects.  Nine infants and young children infected with HIV and 69 seropositive

but uninfected infants and children, age 6 weeks to 45 months.

Results.  Mean Early Language Milestone Scale, 2nd edition (ELM-2) Global

Language scores were significantly lower for subjects with HIV infection,

compared with uninfected subjects (89.3 vs 96.2, Mann-Whitney U test). The

proportion of subjects scoring >2 SD below the mean on the ELM-2 on at least one

occasion also was significantly greater for subjects with HIV infection,

compared with uninfected subjects (4 of 9 infected subjects, but only 5 of 69

uninfected subjects; Fisher's exact test). Seven of the 9 subjects with HIV

infection manifested deterioration of language function. Four manifested

unremitting deterioration; only 1 of these 4 demonstrated unequivocal

abnormality on neurologic examination. Three subjects with HIV infection and

language deterioration showed improvement in language almost immediately after

the initiation of antiretroviral drug treatment. Magnetic resonance imaging or

computed tomography of the brain were performed in 6 of 7

infected subjects with language deterioration, and findings were normal in all

6. ELM-2 Global Language scaled scores showed good agreement with the Bayley

Mental Developmental Index or the McCarthy Global Cognitive Index (r = 0.70).

Language deterioration, or improvement in language after initiation of drug

therapy, coincided with or preceded changes in global cognitive function, at

times by intervals of up to 12 months.

Conclusions.  Language deterioration occurs commonly in infants and young

children with HIV infection, is seen frequently in the absence of abnormalities

on neurologic examination or central nervous system imaging, and may precede

evidence of deterioration in global cognitive ability. Periodic assessment of

language development should be added to the developmental monitoring of infants

and young children with HIV infection as a means of monitoring disease

progression and the efficacy of drug treatment.

J Pediatr Psychol. 1996 Jun;21(3):379- 400.

    Impairment of expressive behavior in pediatric HIV-infected patients with

evidence of CNS disease.

        * Moss HA, Pediatric Branch, National Cancer Institute, Rockville Pike,

Bethesda, land 20892, USA.

    Rated observations of videotapes were made of 16 variables representing 5

behavioral domains (task orientation, positive social-emotional, motor skills,

expressive speech, and activity) on a sample of 83 HIV-infected children.

Comparisons were made on the rated behaviors between children classified as

either encephalopathic or nonencephalopathic. Analyses were conducted separately

for infants (M age = 1.80 years) and older children (M age = 5.15 years). The

nonencephalopathic infants exhibited higher activity levels and were superior in

motor and verbal skills and showed more social and emotional responsiveness than

did the encephalopathic group. The older nonencephalopathic children functioned

in a more adaptive and appropriate manner than did the encephalopathic children

in all domains of behavior. Independently made Q-sort ratings of behaviors

during developmental testing were highly correlated with conceptually congruent

ratings of the

videotaped behaviors.

    PMID: 8935240 [PubMed - indexed for MEDLINE]

Pediatrics. 1995 Jan;95(1):112- 9.

    Differential receptive and expressive language functioning of children with

symptomatic HIV disease and relation to CT scan brain abnormalities.

        * Wolters PL, Pediatric Branch, National Cancer Institute, National

Institutes of Health, Bethesda, MD, USA.

    OBJECTIVES. To investigate the effect of HIV disease on the receptive and

expressive language of children and the relationship between CT scan brain

abnormalities and language functioning. METHODS. Thirty-six children (mean age,

5.5 years; range, 1 through 10 years; 75% vertical transmission; 58% classified

as encephalopathic) with symptomatic HIV infection and 20 uninfected siblings

(mean age, 7.8 years; range, 3 through 15 years) were administered an

age-appropriate comprehensive language test assessing both receptive and

expressive language (Reynell Developmental Language Scales or Clinical

Evaluation of Language Fundamentals- -Revised) . Each HIV-infected child had a

CT scan of the brain as part of the baseline evaluation, which was rated

independently and blindly by two neurologists, for presence and severity of

brain abnormalities using a semiquantitative rating system. RESULTS. Expressive

language was significantly more impaired than

receptive language in the overall sample of HIV-infected children. The

encephalopathic children scored significantly lower than the non-encephalopathic

children, however, the degree of discrepancy between mean receptive and

expressive language scores was not significantly different between these two

groups. The uninfected sibling control group did not have a significant

discrepancy between receptive and expressive language, and they scored

significantly higher than the infected patient group. Greater severity of CT

scan abnormalities was significantly correlated with poorer receptive and

expressive language functioning in the overall HIV-infected sample and a higher

discrepancy between receptive and expressive language in the encephalopathic

group. CONCLUSION. Pediatric HIV disease is associated with differential

receptive and expressive language functioning in which expressive language is

significantly more impaired than receptive language. The sibling

data and CT scan correlations suggest that the observed language impairments are

associated with the direct effects of HIV-related central nervous system

disease.