Disease-specific findings
For most illnesses, early studies have typically focused on the relationship
between disease processes and broad cognitive parameters, such as intelligence
and academic achievement. With further research, more circumscribed components
of ability, such as memory, language, attention, visuospatial, and visualmotor
skills are considered. The cognitive domain of executive functioning, which
includes skills such as organization, planning, problemsolving, multi-tasking,
and self-regulation, has attracted particular interest recently in children with
the following illnesses.
Diabetes. Type 1 diabetes mellitus (T1DM) in childhood has
been associated with deficits of motor and visual motor skills, attention,
memory, and executive functions. These deficits tend to be most pronounced in
children with early age of onset, recurrent hypoglycemia, and longer disease
duration. There is evidence to suggest that the preschool years constitute a
particular period of vulnerability for cognitive deficits in T1DM.
Kidney disease. Children with chronic renal failure are more
likely to experience intellectual delay than unaffected peers and are at risk
for impairments of verbal memory and learning, visual-motor skills, visuospatial
ability, attention, and mental speed. End-stage renal disease conveys particular
risk for cognitive impairment, which may show improvement after
transplantation.
Liver disease. Chronic liver disease in childhood has been
linked to delays in intellectual abilities, language, visuospatial skills, and
academic achievement (especially in math). Outcomes are variable, with some
children functioning within the average range or better, and others who are
significantly delayed. Early disease onset is most clearly associated with poor
intellectual outcome. Smaller growth parameters also predict lower functioning,
especially in younger children, due to disease-related nutritional
deficiency.
Immune disease. Preliminary studies of pediatric systemic
lupus erythematosus suggest association with deficits of intellectual, academic,
visual memory, and executive skills. However, studies to date have not fully
controlled for demographic factors that could contribute to these findings.
Cognitive outcomes have not yet been examined in other immune disorders, such as
juvenile rheumatoid arthritis and juvenile dermatomyositis.
Heart disease. Studies of cognitive outcomes in children
with congenital heart disease (CHD) have implicated deficits of intelligence,
attention, visual-motor skills, academic achievement, and executive functioning.
Mean IQ scores of pediatric CHD samples often fall within the normal range,
though they are typically below the mean of the general population. Greater
impairments have been reported in children with cyanotic as opposed to
noncyanotic cardiac lesions. Transplant recipients incur additional risk
associated with cardiopulmonary bypass during surgery.
Thyroid disease. Congenital hypothyroidism (CH) has been
associated with intellectual impairment and deficits of fine motor skills,
memory, and sustained attention. Academic outcomes are variable, with deficits
of math skills noted in some samples, but normal range achievement in others.
Early identification and treatment are critical to ameliorating cognitive
functioning and enhancing school performance in children with CH.
Solid organ transplantation. Research to date suggests
variable and complex outcomes following organ transplantation. Though memory,
attention, and reaction time have been shown to improve following kidney
transplant, similar effects have not been clearly demonstrated in liver or heart
recipients. Early disease onset, disease-related malnutrition, and poor
pre-transplant functioning have been identified as factors predicting poor
postsurgical outcome. Other factors associated with the transplantation process
itself (eg, infection, rejection episodes, use of immunosuppressants and
corticosteroids) may also negatively impact cognitive functioning, although
these effects are not as well delineated in children as in adults.
Common threads across illnesses
Despite their frequent use in studies of cognitive outcome in pediatric
illnesses, measures of intelligence are relatively insensitive indicators of
disease-related cognitive change. This reflects the fact that intelligence is,
by definition, a stable mental trait. In general, mental activities requiring
active manipulation (eg, learning, attention, math calculations) tend to be more
sensitive than skills (eg, reading decoding) that are practiced to the point
that they become automatic or "overlearned." The term "crystallized" is
sometimes used to describe overlearned skills or knowledge, which are contrasted
with "fluid" abilities requiring active mental manipulation. The ability to
complete academic tasks under time constraints (academic fluency) is often a
useful indicator of disease-related change, when contrasted with the ability to
demonstrate academic skills without time limitations.
Across illnesses, deficits of abilities such as attention, executive
functions, and memory/learning are commonly reported, even in the context of
relatively mild disease. Difficulties with visual-motor and perceptual motor
abilities are also sometimes seen, particularly on timed tasks. Cognitive speed
and work efficiency also are often reduced. While the specific mechanisms
causing these effects are largely unknown, it is generally felt that the
complexity of brain systems underlying fluid mental abilities make them
especially vulnerable to systemic illnesses. In contrast, automatic skills, such
as reading, vocabulary, and structural aspects of language (eg, grammar) tend to
remain intact andrelatively insensitive to disease-related change.
A distinction applied to some chronic illnesses contrasts components of
cognitive dysfunction that are reversible with components that are irreversible.
In chronic renal failure, for example, a stable and often progressive component
of cognitive deficit may emerge, which appears to reflect cumulative and
irreversible disease-related brain insult. At the same time, fluctuations of
ability have also been demonstrated in renal failure that correlate with acute
disease symptoms or treatment (eg, hemodialysis), representing a distinct and
reversible component of cognitive impairment.
Factors mediating cognitive outcome
Age of disease onset or timing of significant disease events can be a
critical factor mediating the cognitive impact of pediatric illnesses. Though
previous models of brain development highlighted the role of plasticity as a
buffer against cognitive deficits after early focal cerebral injury, it has
become increasingly clear that young brains are highly vulnerable to systemic or
generalized insult. For example, research has clearly shown that children below
3 years of age who receive cranial radiation or chemotherapy fare much worse
intellectually than those who receive treatment at an older age. This principle
appears to hold for other forms of brain injury as well and must be considered
in systemic illnesses that impact cognition in childhood.
Cognitive outcome may also be mediated by disease duration, in that the
longer a child has had active disease, the higher the risk for adverse events to
occur, or for the cumulative impact of illness to result in irreversible brain
dysfunction. This point highlights the crucial role of effective medical
management, particularly early in life, in preventing damage to the brain if
possible, and acting quickly to minimize the impact of brain insult if it
occurs.
Disease severity may also influence cognitive outcome. Although not a
universal finding, increased disease severity tends to be associated with
greater cognitive deficits (eg, end stage organ disease and signs of
encephalopathy). In some illnesses, these deficits unfold over time and may wax
and wane with the course of a child's disease, depending in part on the
effectiveness of interventions. A stepwise decline may be seen in diseases
subject to discrete adverse events (eg, heart disease).
A final point worth mentioning has to do with the context of normal
developmental expectations that evolve as a child gets older, and the concept of
"growing into deficit." An illustration of this principle is the child who,
despite underlying vulnerabilities of mental speed and efficiency, is able to
function adequately at school in the early elementary years, when learning is
externally structured and largely based on repetitive drill. Such children
sometimes do not show obvious difficulty until they reach middle school and are
faced with increased expectations for performance speed and efficiency, even
though their disease status has not changed. In these instances, the apparent
"decline" in functioning actually reflects the fact that the child has reached
an age at which new academic demands begin to tap areas of cognition that were
always deficient.
Monitoring cognitive sequelae
The clinical history is an appropriate starting point for monitoring the
cognitive sequelae of systemic pediatric illnesses. Particular attention should
be directed to concerns expressed by parents and educators in the following
areas:
. Difficulty following through or completing tasks
. Reduced work efficiency
. Absent-mindedness/forgetfulness
. Difficulty completing independent academic work, including homework
. Misplaced schoolwork or work materials
. Messy/disorganized workspace
. Difficulty with work that requires organized task strategies, such as
homework, studying for tests, or expository writing
. Slow work speed, difficulty completing tests within the time allotted
. Academic work requires more time or effort than peers
. Homework requires considerable assistance from parents
. Greater vulnerability to fatigue than peers
. Decline in academic functioning from previous level
. Difficulty assuming age-appropriate responsibilities related to disease
management
Some of the difficulties faced by children with systemic pediatric illnesses
resemble cognitive features of attention deficit hyperactivity disorder (ADHD),
although deficits of intelligence and other discrete mental abilities (eg,
memory, visual-motor skills) should also raise the physician's index of
suspicion for systemic illness-related cognitive dysfunction. Often, the pattern
of deficits seen in a child reflects an underlying cognitive vulnerability
independent of pediatric illness (eg, inherited reading disability), exacerbated
by disease-related cognitive effects, such as reduced mental speed and
efficiency. The complexity and variety of cognitive presentations often warrants
exploration by a child neuropsychologist with experience in chronic pediatric
illnesses.
If a problem is suspected
Often, the first signs of pediatric illness-related cognitive dysfunction are
noted by parents and educators in the academic setting. However, the possibility
of a connection between a child's chronic illness and cognitive dysfunction may
be overlooked by educators unfamiliar with the child's medical condition and
treatment. Parents should be counseled to discuss their concerns about their
child's functioning and medical history with teachers. At this stage, it is
sometimes possible for informal modifications to be made that are quite helpful
to the child. It is important for parents and educators to monitor the child's
response to these modifications, to ensure that they are effective.
If informal academic modifications do not result in improvement, parents
should request a case study through their child's school district to formally
determine his/her eligibility for special assistance. If the child is found
eligible for services under a disability designation (eg, learning disability,
speech/language impairment), a plan for service called an Individual Educational
Plan (IEP) is designed to address the child's disability as it interferes with
academic functioning.
An important disability designation for children with chronic illnesses is
"other health impairment" (OHI). OHI refers to a health problem that negatively
affects educational performance and may apply to any of the conditions discussed
above. A brief written communication from the physician, documenting the child's
medical condition, can be extremely helpful in qualifying a child for the
designation of OHI, if functional academic impairment that can be attributed to
the child's illness exists.
The cognitive effects of pediatric systemic illnesses are sometimes subtle
and complex, and may be difficult to discern without the use of specialized
assessment techniques. The challenge of identifying deficits in bright children
can be particularly great, as they may employ compensatory strategies that
effectively conceal their deficits from others. When standard academic case
study methods do not provide the information necessary to design an effective
educational service program, consultation with a pediatric neuropsychologist may
be helpful. In some instances, the neuropsychologist may be able to offer
appropriate intervention recommendations based on a review of history and
existing psychological and psychoeducational evaluation results. Otherwise, a
comprehensive neuropsychological evaluation may be conducted to obtain a
thorough understanding of the child's cognitive limitations and strengths. In
addition to facilitating educational programming, neuropsychological assessment
can assist the physician in monitoring cognitive functioning as an index of the
child's illness. Such assessment may also help the physician and parents to
understand the child's ability to participate in essential medical care.
Conclusion
Many systemic pediatric illnesses place children at risk for cognitive
deficits that can adversely affect functioning in academic and other performance
contexts. The nature of cognitive risk varies with illness type, chronicity,
severity, duration, and age of onset. Performance deficits on tasks tapping
attention, learning and memory, and mental speed and efficiency are common and
tend to be sensitive indicators of adverse central nervous system effects. The
pediatric clinical history is an appropriate starting point for identifying
cognitive difficulties, which are typically first noted in school settings. A
special education evaluation is often helpful in identifying the academic impact
of illness-related cognitive dysfunction and designing appropriate
interventions. Neuropsychological evaluation can be particularly useful in
characterizing pediatric illness-related cognitive deficits and can also assist
in tracking disease status.
F O R F U R T H E R R E A D I N G
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