Pediatric Neurology Quick Talks Neurodegenerative Disorders Michael Babcock Summer 2013 1

Scenario -2 yo female -parents bring child to clinic due to speech concerns -does not say any words -he sat at 7 months, began walking at 16 months, though has not walked for last 2 months -does not make as good eye contact as before -has recurrent episodes where he will staring with behavioral arrest

Developmental Regression -This is not the kid that has recently learned how to walk, though has stopped with an intercurrent febrile illness -Developmental regression is persistent and un-yielding decline in developmental skills -Can also be seen in a child that has a persistent decrease rate in attaining milestones or who has a prolonged plateau.

Differential diagnoses -Neurodegenerative -Grey matter disease -white matter disease -Mitochondrial disorders -Inborn errors of metabolism -Others -infectious -iatrogenic -hearing loss -epilepsies – ESES -toxins -trauma -vascular -endocrine -neoplastic -nutritional -PDDs – Autism spectrum disorder.

Neurodegenerative disease -White matter disease -Early signs -Spasticity/Babinski -Peripheral neuropathy -vision decline – optic nerve atrophy -ataxia -Late: -cognitive decline -seizures -Grey matter disease -Early signs -Behavior change -Cognitive decline -Seizures -vision decline -retinal degeneration -Late signs -spasticity/babinski

History -Good Early life history – pregnancy (infections, medications), delivery (complications), birth-weight, early weight gain, early milestones. -Good develomental history – gross motor, fine motor, speech, hearing, vision. -Social history – Pb risk, risk for nutritional deficiency -Family history – Pedigree, ethnic background

SIGN/SYMPTOM Differential Diagnosis Macrocephaly Fragile X syndrome, Alexander’s disease, hydrocephalus, metachromatic leukodystrophy Microcephaly Angelman’s, Craniosynostosis, CNS malformation, injury, infection, Rett’s Coarse facial features Mucopolysaccharidoses Hepatomegaly Inborn Error of Metabolism, Wilson’s Abnormal Skin Adrenoleukodystrophy, NF1, Sturge-Weber, Tuberous sclerosis, Waardenburg’s, PKU Abnormal Hair Menkes’, PKU, Homocystinuria, Hypothyroidism, mucopolysaccharidoses Abnormal Hearing CHARGE Syndrome, Down Syndrome, Pfeiffer’s Syndrome, Canavan’s leukodystrophy, Smith-Magenis, Velocardiofacial and DiGeorge Syndrome Ocular abnormalities Tay-Sachs, Congenital Syphilis, CHARGE syndrome Genital abnormalities Noonan’s, Fragile X syndrome

Leukodystrophies -Adrenoleukodystrophy -X-linked recessive -symptoms usual stat by age 4-10 -loss of previously acquired neurologic abilities, hyperactivity, seizures, ataxia -Adrenal gland failure (Addison type) -Diagnosis made by detection of VLCFA -MRI shows white matter abnormalities -Tx: dietary restriction of VLCFA, +/- Lorenzo oil, BMTx Metachromatic Leukodystrophy -AR -onset 12-24 months (infantile), or 4- 12 years (juvenille) -deficiency in aryl sulfatase A -accumulation in lipid sulphatide in myelin sheath, brain, peripheral nerve -cognitive function affected initially, followed by motor difficulties and dysarthria -Tx: symptomatic, ? BMTx

PREP Question Of the following, the MOST appropriate next step is: A 5 year old boy presents for evaluation of problems with impulsivity and hyperactivity. His teacher had asked if he might have ADHD. According to the boy’s mother, he has had progressive behavioral problems and is having trouble constructing and building with toys. No behavioral problems were noted in preschool. The family history is negative for ADHD and moss disorders. The mother reports no disruptive changes at home or school. On PE, you note normal mental status and cranial nerves, crossed adduction when eliciting patellar reflexes and sustained clonus at both ankles. Of the following, the MOST appropriate next step is: A. Observation with re-evaluation in 6 months B. Referral to neurology for diagnostic evaluation C. Referral to physical therapy for gait spasticity D. Referral to psychiatry for medication consultation E. Referral to psychology for psychoeducational evaluation

B. Referral to neurology for diagnostic evaluation -Abnormal neurologic exam -most common disruptive behavior in school age children is ADHD -BUT do a thorough neuro exam Crossed adduction Sustained clonus -Emergent evaluation is not indicated -Adrenoleukodystrophy: Demyelinating; onset~7yrs; poor executive function, emotional lability after a period of normal develoment; X-linked, ABCD1 gene, defective oxidation of LCFA in peroxisomes, and they accumulate in myelin, adrenal glands, etc. -Regarding other choices: A. observation with reevaluation: progressive symptoms, abnormal exam C. Referral to physical therapy: evaluation of cause first D. Referral to psychiatry: neuro exam findings indicate underlying process other than ADHD E. Referral to psychology: Same as D

References -Uptodate articles -Review article: The Inherited Neurodegenerative Disorders of Childhood: Clinical Assessment. Percy, A.K. 1987. Bradley: Neurology in Clinical Practice, 5th Ed. 2008 Butterworth-Heinemann. Current Management in Child Neurology. Bernard Maria. Clinical Genetic Evaluation of the Child with Mental Retardation/Developmental Delay