8 Neurofibromatosis 1 (NF1) impacts brain development in ways that researchers are still trying to understand. About half of all people with NF1 manifest some type of cognitive impairment, also known as a learning disability. This does not mean that people with NF1 are not intelligent. In fact, both the medical and legal definitions of learning disabilities require that someone be of average or above-average intelligence. Individuals diagnosed with NF1 are significantly more at risk than the general population for developing a learning disability or behavioral disorder such as attention deficit disorder (ADD), and slightly more at risk for mental retardation. In fact, cognitive impairment is the most frequent manifestation of NF1 during childhood and often the biggest concern for parents. Fortunately, science has punctured many of the longstanding myths about the cognitive abilities of children with NF1, and there are resources to assist people with the disorder in striving to reach their potentials. This chapter reviews the cognitive profile of people with NF1, shows how cognitive impairments may be revealed in learning or behavior, and provides practical advice on how to obtain help for someone who has learning disability. Scientific understanding about the frequency and nature of cognitive disability in people with NF1 has changed markedly during the 1990s. Although children with NF1 have, on average, an IQ that is lower than the average for the general population, some children with NF1 are of average or above-average intelligence.1(p1122) Children with NF1 have a mean IQ (the arithmetic average) between 89 and 94 according to various studies,2–4 compared with the general population range of 90 to 110. Researchers have not found any correlation between IQ and other NF1 manifestations, gender, or socioeconomic status. One team did find that IQ for children with NF1 increased with age, rising from an average of 90 in children between the ages of 6 and 17, to 99.3 for those 17 years or older.5 Other studies, though, suggest that there is no improvement in IQ3 or overall cognition6 with age. This remains an issue requiring further investigation. Studies conducted decades ago overestimated the incidence of mental retardation in persons with NF1. Usually the researchers relied on data collected from institutionalized patients and therefore did not include individuals with NF1 living in the community who had milder manifestations of the disorder.1(p1121) About 3% of people in the general population are born with global developmental delay (mental retardation),1(p1121) defined as an IQ that is less than 70. Studies done in the past two decades have reported that anywhere from 3% (based on a population-based study)7 to 5 to 8% (based on IQ measurements made in the clinical setting)2,3,8 of children with NF1 have global developmental delay. Thus, children with NF1 are somewhat more likely to be mentally retarded than the general population, but the risk is not as great as once feared. Many children with NF1 have some type of cognitive impairment, however. A cognitive impairment is a defect in any brain function, such as the ability to pay attention or process sounds and other aspects of language, which in turn alters the capacity to think and learn. For this reason, cognitive impairment often manifests as a specific learning disability. This general term refers to any one of several hindrances to learning that are not caused by some underlying loss of sight, hearing, motor deficit, mental retardation, or the like. For instance, a child may have normal eyesight and muscle strength, yet have an impairment in the brain’s ability to integrate visual input with motor skills. This can result in difficulty with handwriting or coordination. Learning disabilities often impede competence in listening, thinking, speaking, reading, writing, spelling, or doing mathematics. A cognitive impairment may also manifest as a behavioral disorder such as ADD. Although often associated with children, both learning disabilities and behavioral disorders can persist into adulthood. Everyone has a unique learning style. Some people are better at math and science, others at languages. Such variations are completely normal and reflect subtle underlying differences in how individual brains function. These differences are considered “dysfunctions,” and therefore cause for concern, when they are pronounced enough to delay brain maturation or age-appropriate skill development. Should this occur, the underlying brain dysfunction has caused a learning disability. Years ago, many children with learning disabilities were dismissed as “stupid” or criticized for not trying hard enough. Others were seen as obstinate and as behavior problems. Some were even characterized as mentally retarded. As research into the brain and different learning styles progressed, however, physicians and educators came to realize that children with learning disabilities are of average or above-average intelligence, but they require some type of assistance or accommodation to learn. These accommodations function somewhat like eyeglasses for the brain: the goal is to adjust for an inborn difference that interferes with learning. Although there are multiple types of learning disabilities, they generally fall into one of four categories: A child with a learning disability may see letters and numbers on a page as upside down or reversed; an “m” might be seen as a “w,” or an “E” as the number “3.” Or the child may be unable to organize schoolwork or follow directions. If a motor impairment is involved, handwriting may be illegible. Estimates of the prevalence of learning disabilities in the general population vary. The Centers for Disease Control estimates that 8% of children ages 6 to 11 have a learning disability, and that half of them have ADD as well.9 Other sources estimate that as many as 20% of people in the United States have a learning disability.10 Whatever figure is used, people with NF1 clearly have a higher incidence of learning disabilities than the general population. Various studies have reported that anywhere from 30 to 65% of children with NF1 have learning disabilities.1(p1122) The variation probably reflects different definitions of what constitutes a specific learning disability, as well as different methods of collecting data. As is typical of the general population, boys with NF1 are more likely than girls with the disorder to have a learning disability. Some of the latest research disputes this discrepancy between boys and girls and attributes it to cultural biases and/or testing methodologies. Children who come from lower socioeconomic groups are also more at risk. The overall consensus is that about half of all children with NF1 develop some type of learning disability.11 Because learning disabilities occur so frequently in children with NF1, it is likely that the NF1 gene mutation may be to blame, although it is not clear how. Neurofibromin exerts its effects in the body by activating certain signaling pathways that direct cell growth and development. Two pathways under investigation for causing learning disabilities are the Ras pathway and the cyclic adenosine 3′,5′-monophosphate–protein kinase A (cAMP-PKA) pathway, which both relate to functioning of neurons in the brain, but in different ways. Researchers studying mice have found, for instance, that excessive Ras activity interferes with the process of learning and memory formation. They theorize that in people with NF1 a similar defect may underlie at least some of the cognitive deficits.12 A competing theory, based on experiments in fruit flies, is that the cAMP-PKA pathway is responsible for learning deficits. Fruit flies genetically engineered to have one malfunctioning NF1 gene are worse at learning to escape from a container than normal flies. They also experience defects in potassium channel function, which determines how well signals are sent between neurons.13–16 Analysis of neurofibromin’s functioning in human brain tissue has provided still other clues. One theory is that neurofibromin helps neurons to send signals to one another, and that a deficiency in the protein may disrupt communication in the brain. Other evidence suggests that neurofibromin contributes to healthy development of particular parts of the brain during the prenatal period.17 Another developmental theory focuses not on neurons, but on glial cells, the myriad support cells in the brain. Glial cells help form the protective myelin sheath around nerves and mop up excess neurotransmitters—which helps neurons to communicate better. Some scientists propose that loss of neurofibromin causes abnormal growth and development of glial cells.1(p1124) The research continues; for now the theories remain speculative. Magnetic resonance imaging (MRI) technology uses radio waves and a strong magnet to produce images of soft structures inside the body, including the brain. Because different tissues emit radio signals of varying intensity, the image that emerges is full of dark and light contrasts, similar to a photograph, that enable brain structures or abnormalities to be seen by someone who is trained to read the scans. Sixty to 70% of children with NF1 have unidentified bright objects (UBOs) visible on MRI brain scans (Fig. 8–1). Technically, UBOs are areas of increased signal intensity on T2-weighted MRI images. They have no mass and are not known to impede function. Although UBOs can appear anywhere, they most often are located in the basal ganglia, optic tracts, brainstem, and cerebellum. UBOs tend to disappear when people with NF1 reach their 20s or 30s.1(p1123) Figure 8–1 An example of an unidentified bright object, or enhanced T2 signal, on magnetic resonance imaging. It is not clear what causes UBOs, although clues are offered by two small studies involving analysis of three brains each. In one, researchers found that brain tissue taken from people with NF1 contained levels of a protein known as gliofibrillary acidic protein (GFAP) that were four to 18 times higher than normal.18 Such dramatically increased levels of GFAP indicate that a process known as reactive astrocytic gliosis—a change in the number, size, and characteristics of the glial cells that normally support neurons—has taken place. Reactive astrocytic gliosis occurs whenever there is an injury, infection, or abnormality in neurons, and it has been observed in neurodegenerative conditions such as Alzheimer’s disease, Parkinson’s disease, and Down syndrome. The other study compared findings on previous MRI studies with analysis of brain tissue on autopsy. The researchers reported that UBOs were found in areas of the brain where there were abnormalities in glial cell proliferation, and the protective myelin sheath had small openings or vacuoles, possibly due to swelling and water retention in the myelin (intramyelinic edema). The scientists theorize that UBOs, therefore, may be caused by excess water content or defects in myelin.19 The research continues. It is also not yet clear what UBOs signify. They are not correlated with overall severity of NF1, specific neurological deficits, or macrocephaly.2,20 Some evidence does suggest that UBOs may have some correlation with cognitive impairment, although this is an area that remains controversial and there is no consensus about specifics. The first studies to examine the question found no relationship between UBOs and cognitive defects. Some critics questioned the scientific methods used, however. Two early studies, for instance, did not consistently measure cognitive function, or even clearly define what skills were being assessed. More recent studies compared detailed medical records, including measures such as IQ scores, with MRI scans. One study found that children with NF1 and UBOs had significantly lower IQ scores than peers with NF1 but without UBOs.2 Another study, comparing children with NF1 to unaffected siblings, found that the number and size of UBOs was highly correlated with lower IQ scores. The size of UBOs seen in the basal ganglia also had some association with the degree of visuospatial abnormalities a child experienced.4,21,22 Several other studies, however, have contradicted these results and found no association between UBOs and lower IQ.23,24 To further muddy the waters, a recent study found that the best predictor of cognitive dysfunction in adulthood was the presence of UBOs in childhood, but that cognition does not improve as the lesions decrease or disappear with age.6 The debate on this issue continues. Generally speaking, there is no “learning disability profile” for a child with NF1, although children with the disorder do tend to be weak in mentally processing spoken and written words, numbers, and achieving visuomotor coordination. Contrary to what was suggested by earlier studies, language-based learning difficulties, such as reading and spelling, are as common as nonverbal learning deficits, such as impulsive behavior and poor organizational skills.2,4,25,26 Children with NF1 tend to perform especially poorly on tests of visuospatial coordination, such as the judgment of line orientation, but many other types of learning disabilities are also common.11 Usually these differences are discovered when the child enrolls in school and has difficulty completing tasks or understanding what is expected. The first sign of a learning disability in preschool children may be clumsiness (if there is a motor difficulty) or speech delays or difficulty (if related to verbal ability).27 None of these learning obstacles reflect poorly on the child’s innate intelligence. As the NF1 Cognitive Disorders Task Force stated in its consensus statement, “Simply put, a [specific learning disability] represents a major discrepancy between ability (intellect or aptitude) and achievement (performance).”1(p1121) Left untreated, learning disabilities can have lifelong impact on education, career, and overall achievement. Fortunately, remedial interventions are effective and often available free of charge through the school system. The most common types of learning disabilities seen in NF1 are briefly described below. Language-based learning disabilities interfere with a person’s ability to hear, see, process, or speak words. This type of disability can limit the ability to listen, speak, read, and write. Specific examples include a tendency to reverse or rotate words and letters (mistaking “dog” for “god”), difficulty distinguishing one word or math problem from others on the page, or incorrect word articulation. Because language is essential to communication, language-based learning disorders can have lifetime impact. They increase a person’s risk of doing poorly in school, at work, and in social situations. Typically people with NF1 who have a language-based learning disability may display the following characteristics: The individual is easily distracted, has trouble listening to someone for an extended period, or may need longer than other people to “process” what is being said. The individual cannot remember grammatical rules or sequences of words. The individual does not understand what he reads, has a limited vocabulary, and does not understand that the same word sometimes has different meanings. This limits the ability to grasp concepts such as metaphors, irony, and ambiguities. The individual finds it hard to understand mathematical word problems or to solve problems verbally. The individual sometimes uses inappropriate language when interacting with others and may misinterpret what another person is saying. The individual is unable to distinguish between similar-sounding sounds and words, and as a result may misunderstand what is being asked. The individual may say something that makes no sense or tell a story in which chronological events are out of order. Nonverbal learning disabilities are those that involve any brain functions other than those involved in processing language. This category also encompasses the brain’s ability to process and integrate multiple streams of information at once. Examples of nonverbal learning disabilities include visuospatial coordination, motor coordination, perception, and attention. The individual may have difficulty with directions or with orienting himself to surroundings. The person may also have trouble reading and drawing maps, charts and graphs, and diagrams. The individual may be clumsy and tend to bump into things or knock items over when reaching for them. The person also has difficulty with some sports that require hand–eye coordination such as baseball or basketball. Certain skills require both verbal and nonverbal abilities. Two notable examples are mathematics and written language. Children with written language disabilities may have poor handwriting, trouble with spelling and grammar, and be unable to compute mathematical equations or solve word problems. Many middle-aged and older adults with NF1 have faced a lifelong struggle with learning disabilities because they grew up and went to school before such disabilities were recognized as clinical entities, and before public schools were required to provide remedial help. Fortunately, both science and public policy have evolved so that children with learning disabilities can receive the help they need to achieve more of their potential. Given the high risk that a child with NF1 will develop a learning disability, parents and physicians alike should be alert for signs that a child is not keeping up with normal developmental milestones (the first word, the first step, etc.) and seek appropriate screening. It is important to remember that learning obstacles may develop at any time during the preschool or school-age period, because the nature of learning disabilities varies greatly in type and severity. Differences in ability become evident in some children early in life, but in others they become apparent only as school or intellectual demands increase with age. If a learning disability is suspected, the child should be evaluated as early as possible by appropriate professionals. Remedial services should be obtained to maximize the child’s ability to learn and minimize the chances of falling behind in school.11 Learning disabilities are usually diagnosed in school-aged children. If a parent suspects a child with NF1 has a learning disability, the first step is to talk with the teacher or school principal to learn what procedures the school has in place. Generally speaking, school officials will conduct standardized tests that measure how the child’s skills and abilities compare with what is considered normal. Parents must first be apprised of such testing and what it will involve. They then provide written permission before it can proceed. Because children with NF1 may have neurological abnormalities, it is important that the child undergo (if he hasn’t already) a detailed neurological examination, ophthalmological exam, and hearing test to rule out these sorts of abnormalities. By the time they reach school, children with NF1 should have undergone all of these tests (see Chapter 5). MRI scans are not recommended as part of a routine diagnostic workup for learning disabilities. These scans may be appropriate when the child has a neurological deficit that suggests the presence of a tumor, intracranial pressure, or some other lesion. After administering the standardized tests, a team of school professionals meets with parents (with the child present, if appropriate) to discuss the results. Generally this team consists of the child’s regular teachers, a special education teacher if applicable, school administrators, and other professionals, such as a speech therapist or school psychologist, as required. This same team also determines the child’s eligibility for special education services. A child is eligible for special education services under the provisions of the Individuals with Disabilities Education Act (IDEA, Public Law 101–476). This 1990 law supplanted an earlier law, the Education for All Handicapped Children Act (Public Law 94–142). IDEA covers private as well as public schools and provides criteria for 13 categories of disabilities that are eligible for services. Children with NF1 generally qualify for services under two categories: “specific learning disability” or “other health impairment.” It is important to note that not all children who have a learning difficulty meet the criteria for a “specific learning disability” under IDEA. Nonverbal learning disabilities, for instance, are not eligible for special education services under this category. Children with NF1 who have nonverbal learning disabilities, or have other learning challenges not classified as specific learning disabilities by IDEA, however, may still be able to receive services because NF1 falls under the classification of “other health impairment.” If it is determined that the child is not eligible for services under IDEA, parents must be informed in writing by the school and provided with information about whom to contact to appeal the decision. If this information is not provided, parents should ask for it. Many school districts apply a narrow interpretation of eligibility to avoid the expense associated with providing special education services. Therefore, parents should expect to fight hard for the services their child needs. Many have to be persistent and act as advocates through a lengthy appeals process. If a child is eligible for services, IDEA stipulates that an individualized education plan (IEP) be developed. An IEP is a written agreement between parents and school officials about what services the child needs. It includes an assessment of the child’s abilities, establishes short-term and annual goals for the child, and details the type of services the child will receive to help attain those objectives. The IEP is reviewed at least once a year to review progress and make further adjustments. (Parents can appeal school officials’ recommendations and findings. Check with the school district for details.) Services and accommodations vary, depending on the child’s needs. Children with weak visuomotor coordination, for instance, may benefit from treatment by an occupational therapist. Children who are not proficient in organizing information or work may need help to break a task into clearly defined steps. Reading skills can sometimes be improved by having the child read out loud, because the part of the brain that processes spoken words is different from the one that interprets written words. Sometimes the child’s teacher can adjust instruction style to meet the child’s needs; at other times a special education teacher or teacher’s aide may be required to provide the assistance. Although school systems are usually the primary source for services, they are not the only resources available. Several national and state organizations exist, some with a broad mission and others focused on selected learning disabilities such as dyslexia. Children with NF1 tend to exhibit troubling behavioral patterns such as acting out at others, inflexibility when confronted with change, or a tendency to become distracted and lose focus. Some of these behaviors may result from frustration at not being able to keep up with peers, especially if the child has a learning disability and is not able to interpret and process information as rapidly or efficiently as other children do. At other times, children with NF1 may act out because of a behavioral disorder—with or without a coexisting learning disability. The most common behavioral disorder in children with NF1 is ADD. According to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), the standard reference used to diagnose psychiatric and behavioral disorders, a person has ADD if six or more symptoms of inattention persist for at least 6 months. Typical symptoms include failure to pay attention, careless mistakes, problems in organizing work, tendency to become distracted, and difficulty listening even when addressed directly.28 If a child is diagnosed with ADD, treatment usually consists of a combination of behavioral interventions and medications. Stimulants are most often prescribed because they activate parts of the brain that are inactive in ADD and help the child to focus. As is the case with learning disabilities, many resources exist to help children with ADD. Parents should consult first with their child’s pediatrician and teacher, and then contact both national and local organizations for more information. Such resources can be located with the help of a local librarian or by conducting an Internet search. Learning disabilities are lifelong disabilities. Some people find ways to compensate for them, but adults with NF1 may continue to endure the consequences of learning disability. In some cases, their cognitive differences were not diagnosed and treated appropriately. Many middle-aged and elderly people with NF1 attended school before such cognitive difficulties were understood, treatment was available, or their treatment mandated by law. Insufficient reading and writing skills bar many adults with learning disability from work they would otherwise be capable of and interested in doing. An adult with learning disability may struggle to keep pace with fellow employees or acquire new skills in the workplace. ADD often persists into adulthood, although this has only recently been recognized. Adults with ADD may make careless mistakes at work, are perceived to be disorganized, or interrupt others in meetings. Learning disabilities and ADD often manifest themselves more subtly in adults than in children. Because of the frustration they experience each day, adults with learning disabilities and ADD may be discontented with personal relationships and may engage in alcohol or substance abuse. Diane D.: “Julie was diagnosed with learning disabilities early on, and more recently with attention deficit hyperactivity disorder (ADHD). She started off in early intervention when she was a year old and then transitioned to the school system. The school has been cooperative. But now with ADHD, things have become more challenging. For the past 4 months, Julie’s been struggling to find medications she can tolerate. And we’re working with the school to see if we can make some adjustments. “We are working with a person outside the school system, a psychologist who specializes in treating ADHD combined with learning disabilities. She’s a tremendous advocate and in close contact with our pediatrician. We’ve come up with a wonderful team. We are in discussions with the school about changing Julie’s learning environment, though. We’ll see how that goes.” Dolores G.: “Susan’s coordination was a bit questionable. She was klutzy, but so am I, so we didn’t think anything about that. She went to preschool and nursery school, and she appeared to be learning well. Her dexterity was bad, but that was attributed to the klutziness. At the time they didn’t know much about learning disabilities. “As she got into middle school, her handwriting was atrocious. Her math and spelling abilities were very bad, but she was a determined child and she made it through. In the fifth grade, she really needed more attention, so we put her into a private school and she went there for 2 years. But the private school wouldn’t accept her to its junior high because academically she wasn’t adequate. She went back to the public school. But they wouldn’t let her enter into her class in junior high. They kept her back a year, which was a real psychological blow to her. “In high school, Susan did well. She got private tutoring for math and had that for many, many years. She graduated from high school, even though she had a lot of surgeries and was out of school a fair amount of time. Susan had a guidance counselor at school. When she was a junior in high school, he told her, ‘Susan, I would suggest that you not try to go to college. You’ll be lucky if you make it through trade school.’ And she looked at him, and said a few choice words, and then said, ‘I am not going to do what you say. You cannot convince me that I’m not going to make it. I’m going to go ahead and take my regular courses.’ “I think it’s important for other families to know this in case they encounter something similar. Susan attended Wright State University in Ohio. It’s a state school that specializes in young people who are challenged. Some have learning disabilities and others have physical disabilities. Susan did well. She went through the whole program and graduated. It took her 5 years, but not because of academic reasons. She had to take time out from class to undergo surgeries.” Tamra M.: “I’ve had some small motor skill difficulties. I have trouble writing, so I type or have kids take notes for me in class. I do fairly well in school. “Last year, I missed practically all of one semester at school because of surgery. I had to wear a head “halo” brace for 8 weeks. I did a home tutoring program and still got credit for all but one of my classes. “I want to go to college. That’s a definite. I want to write. I like to write. I write poetry and fantasy, like Lord of the Rings. I am taking a creative writing class now, and am enjoying it. It’s fun. I’ve had two poems published. One was in an NF newsletter and the other was in my school’s magazine.”
Cognitive Function and Learning Disabilities in Neurofibromatosis 1
♦ The Neurofibromatosis 1 Cognitive Profile
♦ Learning Disabilities: Myths and Realities
♦ An Overview of Learning Disabilities in Neurofibromatosis 1
Pathology of Learning Disabilities
The Debate About Unidentified Bright Objects
♦ Types of Learning Disabilities in Neurofibromatosis 1
Language-Based Learning Problems
Poor Listening Skills
Faulty Word Memory
Limited Reading and Word Comprehension Skills
Difficulty in Verbal Reasoning
Impaired Verbal Social Skills
Trouble Distinguishing Sounds
Disorganized Communication Skills
Nonverbal Learning Disabilities
Visuospatial Coordination
Visuomotor Coordination
Mixed Learning Disabilities
♦ Management of Learning Disabilities in Neurofibromatosis 1
♦ Behavioral Problems
♦ When Problems Persist into Adulthood
♦ The Personal Perspective
References
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