Neuropsychological Aspects of NF1

Joe Ackerson, Ph.D.Clinical Director

Ackerson & Associatesjackerson@ackersonandassociates.com

What is Neuropsychology?

• A subspecialty of Clinical Psychology• Specializing in understanding Brain-Behavior

Relationships• Applies this knowledge to promote adaptation in

the individual• Pediatric Neuropsychology emphasizes a

developmental framework and addresses academic and family issues.

Relevance of Neuropsychology

• Ability to demonstrate change• Rule out alternative explanations• Describe neurocognitive profile• Identify moderators of functional outcomes• Promote realization of one’s future potential

Adaptation• The central goal of neuropsychology is to

promote adaptation and functioning• Adaptation results from interactions between

individuals and their environments• Failures in adaptation may be seen as a matter

of a “lack of fit” between the individual and their world

Understanding Brain and Behavior

• Analysis of brain-behavior relationships provides insights into adaptation

• Brain-behavior relationships can be both one-to-many and many-to-one

• Understanding these relationships provide a framework for organizing findings

• Any complex behavior reflects multiple brain systems

Making Predictions • A thorough history is essential (know

the past to tell the future)• Assessment should help anticipate

the future, not just describe present• Explain adaptive failures and predict

risk in terms of mismatch

Impact of NF1 on the Developing Brain

• Defining NF1

• Domains of functioning

• Recommendations for success

NF1

• Common autosomal dominant, genetic disorder.• Multi-system: neurological (central and

peripheral), cutaneous, skeletal, and neoplastic manifestations.

• Increased risk of developing tumors of the central and peripheral nervous system.

Clinical Presentation

• Genetic mutation that can affect ANYONE.

• Early childhood, puberty and childbearing age in females are considered to be the periods of greatest risk for disease progression

• NP symptoms of NF1 vary greatly and may not appear school age or later.

• No cures (yet)

Neuropsychological Aspects of NF1

• Learning disorders (LD) are the number one morbidity of NF1, affecting 50-65%.

• A wide range of LD can be seen including ADD, ADHD, Reading (dyslexia), Math, Nonverbal LD, and Written Language.

• Can lead to lifelong academic and occupational underachievement, behavioral, and emotional problems

• General intelligence and other cognitive functions can be completely spared.

NF1, LD, and the RAS Pathway

• Learning problems in NF1 may be related to Ras function. • Studies suggest that an upregulation of Ras activity may

account for the LD in both mice and humans with LD. • A mouse model suggests excessive Ras activity leads to

long term potentiation (LTP) deficits.• LTP + the neural basis of learning, think of a “neural

pathway• So LTP deficits lead to learning and attention problems. • We have developed Neuropsychological protocols to better

understand the impact of NF1 and some of the proposed treatments.

Neurocognitive functioning in NF1

• Hyman 2005 study of 81 children aged 8-16• Up to 81% of children with NF1 demonstrated

significant deficits on some measure of cognitive functioning

• 63% demonstrated problems with attention but only 38% met formal criteria for a specific learning disorder (SLD)

• 51% demonstrated significant deficits in academic functioning (reading, writing, arithmetic)

• But only 20% met formal criteria (under significant discrepancy model) for a specific learning disability

There is NO specific Neuropsychological profile but…

• Executive, attention, and visuospatial skills tend to be the most affected

• Expressive and receptive language also affected• Memory functioning may be relatively spared

Current Lovastatin Research

• Applying a mouse model of NF related visuospatial learning (Li et al, 2005)

• Statin drugs appear to influence the Ras pathway• Lovastatin reversed the spatial learning deficits in

mice• Current study underway through the NF

consortium studying the possible impact of Lovastatin on attention, memory, and learning problems in children

• Proposed mechanism different from stimulant medications for ADHD

Domains of Functioning

• Intelligence• Executive functioning

– Arousal and Speed/Efficiency

– Attention/persistence

– Self-regulation/motivation

– Problem-solving/flexibility

• Language• Visuospatial/Visuomotor• Memory• Academic

When to test?

• Early identification means early treatment• Early treatment associates with better outcomes• Early reading problems predict later reading

problems• Reading is key to academic success

Assessing individual clients

• Determine medical & nonmedical variables• Assess neuropsychological functioning• Identify risk within environmental context• Predict functional outcomes• Provide recommendations for management

Arousal problemsArousal problems• Antidepressant, activating, or sleep aid

medication• Encourage sleep routine in evening• Intersperse structured activity with rest periods• Graduated program to develop endurance and

ensure success• More demanding interventions/classes in morning

Attention problemsAttention problems• Stimulant or similar acting medication• Reduce distractions• Self-monitoring techniques• Rewards for task completion• Hands-on, participatory instruction• Close monitoring and redirection

SlowingSlowing

• Activating medications• Adaptive techniques to minimize required

effort• Reduce pace of instruction and amount of

work • Evaluate quality, not quantity• Limit homework• Allocate more time for activities

Executive function deficitsExecutive function deficits• Direct instruction in decision-making and self-

regulatory skills• Structure and organize• Routine and predictability

– Break tasks into manageable steps

– Need for frequent feedback

• Focus on process, not just outcome

Nonverbal/Visuospatial deficitsNonverbal/Visuospatial deficits• Teach to verbal strengths• Reduce visual complexity, less clutter• Use familiar and readable materials and tasks• Increase print size & have fewer problems per

page• Use step-by-step approach, build on practice and

review

Visuospatial (cont.)

• Use visual guides (finger, ruler) to keep place• Use lines or large block graph paper to maintain

alignment• Highlight important text• Trace the operand (sign) in Math equations

Memory deficitsMemory deficits• Mnemonic/learning strategies• Frequent repetition and review• Environmental aides• Homework assignment book• Activity schedules• Regular routines• Cueing

Emotional (Mood) Concerns

• Natural adaptation to illness• Anxiety• Grief and coping with perceived versus actual

loss• Clinical depression

Evaluation and Modification

• Is it working? • Why not? • Understanding failure.• Building on success.

Develop transitions orbridges between key points.

Family supportFamily support

• Anticipatory guidance and follow-up• The family functions as part of the treatment

team• Train yourself up as advocates• Know when to fight and when to play well with

others

Resources

• UAB Genetics Clinic (www.genetics.uab.edu)– (888) 822-4362 or (205) 934-5567

• Neurofibromatosis, Inc. (www.nfinc.org)• The Children’s Tumor Foundation (www.ctf.org)

• Alabama Dept of Special Education– www.alsde.edu

• Alabama Disabilities Advocacy Program– www.adap.net

Questions?