Even More PREP Questions

1. Even More PREP Questions Neurology Rotation Lecture Series Last Updated by Lindsay Pagano Summer 2013

2. PREP question A 5 month old girl presents with a 1 week history of exaggerated startle movements and decreased motor and social activity. According to her parents, the child bends her head and trunk forward, extends her arms out quickly, and cries. Such actions may occur 10 to 20 times consecutively and have become more frequent over the past several days. She has also is much less physically active and less interactive with her patents. EEG shows a diffuse, severely abnormal pattern (hypsarrhythmia). • Adrenocorticotropic hormone • Carbamazepine • Phenobarbital • Phenytoin • prednisone

3. A. Adrenocorticotropic hormone Infantile Spasms (IS) • Additional treatment option: vigabatrin (Sabril), high dose topamax • Bridging therapy with steroids versus topamax • FYI re EEG: hypsarrhythmia is NOT the seizure • Subtle seizures, cluster, “clasp knife” is a catch phrase description • Important to also evaluate for developmental delay, syndromes (eg TSC) • Prognosis is dependent on if there is preexisting delay or neurologic disorders • Regarding the other choices: B. carbamezepine: not effective for IS C. phenobarbital: sedating, not as effective D. phenytoin: not effective for IS E. prednisone: not long term tx

4. PREP question A 2 ½ year old boy is not yet saying any words. His parents are worried that he is not developing like his peers and are concerned that he is not yet talking. Other than two episodes of otitis media in the past year, he has been in good health. A formal audiology evaluation reveals normal hearing. His head circumference is at the 90th percentile; his weight and height are at the 75th percentile. PE is normal. His father did not talk until he was 3 years old. Of the following, the MOST appropriate next step is to: • Order electroencephalography • Order head magnetic resonance imaging • Reassure the parents and have the child return in 6 months • Refer the child for developmental evaluation • Refer the child for neurologic evaluation

5. D. Refer the child for developmental evaluation • Speech delay • Family history of delay • Evaluation for delay in other areas • Regarding the other choices: A. EEG: no regression B. MRIbrain: normal, nonfocal neuro exam C. Reassurance and return in 6 months E. Refer to neurology: no regression

6. PREP question At a routine health supervision visit, the parents of a 12 year old boy report that their sons walking and running seem to have become clumsy over the past few years. He reports no pain in the legs or back, and there is no family history of neurologic problems. PE reveals no abnormalities of joints, muscles or skin. Mental status, speech and cranial nerves are normal on neurologic examination. Arm strength, reflexes and coordination are normal. Strength in his feet is slightly diminished, and reflexes at the knees and ankles are absent. No muscle wasting is apparent. He has a slightly broad based, unsteady gait and has great difficulty with tandem gait. He exhibits significant postural sway with his eyes closed and feet together (Romberg). Of the following, the MOST likely explanation for these symptoms is: • Ataxia telangiectasia • Dandy Walker syndrome • Friedreich ataxia • Hydrocephalus • Multiple sclerosis

7. C. Friedreich ataxia Ataxia • Axial versus appendicular: how to assess? • Localization possibilities: cerebellar peduncles versus hemispheres versus vermis (as long as true ataxia, not due to weakness, sensory disturbance) • Discrete episodes versus progressive deficit, acute versus subacute • Family history! • Other defecits, dysmorphisms or cutaneous findings • Most common in children: • Friedreich ataxia: AR; frataxin gene > 90 GAA repeat expansion • Ataxia telangiectasia: AR; neuro findings before derm findings, but should have skin findings by 12 yo • Spinocerebellar ataxia 1, 2, 3, 7: AD • Regarding the other choice: A. Ataxia telangiectasia: no cutaneous findings B. Dandy Walker syndrome: no progressive D. Hydrocephalus: should have other signs/symptoms, eg HA, hypereflexia E. Multiple sclerosis: shouldn’t have a fixed/progressive deficit

8. PREP question You are seeing a 4 year old boy who is new to your practice for a health supervision visit. While reviewing the family history, you learn that his father has neurofibromatosis type 1. Careful examination of the boy’s skin using a Woods lamp reveals six café au lait macules measuring at least 5 mm, but no other lesions. Of the following, the MOST likely feature(s) of NF1 to develop next in this boy is (are): • Cutaneous neurofibromas • Lisch nodules • Plexiformneurofibromas • Pseudoarthrosis of the tibia • Skinfold freckling

9. E. Skinfold freckling NF1 • 1/3000 • 80% have at least 6 café au lait macules by 5 years old (number and size change over time) • Skinfold freckling typically by age 3-5 year old • Neurofibromas are third to appear • Lisch nodules may not appear until adulthood • 25% with plexiformneurofibromas, often congenital • Tibialpseudoarthrosis is either congenital or occurs following fracture due to congenital bowing • By 11 years old, 95% of affected individuals will have clinical diagnostic criteria • Regarding the other choices: A. Cutaneous neurofibromas B. Lisch nodules C. Plexiformneurofibromas D. Pseudoarthrosis of the tibia

10. PREP question You are called to the nursery to evaluate a 12 hour old infant for episodes of jerking. She had been born following a term pregnancy. Vaginal birth was being attempted after a prior cesarean section. Fetal monitoring had shown an apparently reassuring heart rate and normal status prior to delivery. After replacing the monitor following transport from the labor to the delivery room, the tracing indicated an abrupt decrease in heart rate. A stat cesarean section revealed that the uterus had ruptured and the infant was out of the uterus and in the abdominal cavity. The baaby required endotracheal intubation and chest compression but not epinephrine. Apgar scores were 1 at 1 minute, 1 at 5 minutes and 5 at 10 minutes. You question the parents and nurse about any possible seizures. Of the following, the description that MOST likely indicates that the child is having neonatal seizures is: • Episodes of bradycardia with apnea • Fatiguing and vomiting during nursing • Focal jerking in both arms simultaneously but asynchronously • Limb jerking triggered by touching the child • Spontaneous limb jerking that stops when a hand is placed on the child

11. C. Focal jerking in both arms simultaneously but asynchronously • Neonatal seizures • Etiologies: HIE, CNS infection, structural malformations, metabolic disease, stroke • Typically focal with one phase (eg tonic or clonic), but hard to discern just based on semiology • Regarding the other choices: A. Episodes of bradycardia with apnea: most of these are not seizure, and not typically isolated findings in seizure B. Fatiguing and vomiting during nursing: not typical of seizurs D. Limb jerking triggered by touching the child: not typically triggered in this fashion E. Spontaneous limb jerking that stops when a hand is placed on the child: abnormal electrical activity to suppressed by physical touch

12. PREP question You care for a 7 year old boy who has moderate intellectual disability and autistic behavior. Molecular genetic testing has confirmed that he has findings consistent with classic fragile X syndrome. His pregnant mother has undergone prenatal testing, which revealed that she is carrying a female fetus that also has fragile X syndrome. Of the following, the MOST accurate statement regarding fragile X syndrome in females is that: • Their affected sons have more severe intellectual disability than their affected brothers. • They can have normal intelligence • They do not exhibit autistic behaviors • They typically are affected as severely as males who have the fragile X syndrome • They are usually infertile

13. B. They can have normal intelligence Fragile X • Dysmorphisms, moderate intellectual disability, autistic features • 1/4000 males • Presentation dependent on age • Prepubertal boys may be large for age with relative macrocephaly, be hypotonic, have GER, have recurrent OM, have motor and speech delay, display behaviors such as hand-flapping and wrist-biting • Over time, their faces elongate, forehead becomes prominent, and ears and jaw become more noticeable • After puberty: macroorchidism • FMR1, progressive expansion of a trinucleotide repeat (CGG) on exon 1 (anticipation) • Normal: 5-40 repeats • Intermediate: 41-58 repeats; no unusual phenotype, unclear significance, rarely show expansion in future generations • “Premutation:” 59-200 repeats; normal intelligence, but may have some features • “Full mutations:” >200 repeats; allele is methylated, silencing FMR1 expression  syndrome expression • Regarding the other choices: A. Their affected sons have more severe intellectual disability than their affected brothers: after reaching 200 repeats, more repeats don’t denote increasing disease severity C. They do not exhibit autistic behaviors D. They typically are affected as severely as males who have the fragile X syndrome: less affected; 50% are intellectually disabled; thought to be due to the ratio of active “normal” Xs to active FMR1 mutated Xs E. They are usually infertile: 20% premutation carriers have premature ovarian failure, but full mutation carriers have normal fertility