A Child with Infantile Spasms Sidharth Puri MD Grand Rounds - March 31, 2017

Patient Presentation CC HPI Persistent seizure like activity 8 yo WF w/ developmental delay who presents with intractable, daily infantile spasm-type seizures. Has been ongoing since ~3 months age and has worsened over past year.

History (Hx) PMHx- Developmental delay, seizures since age of ~3 months, was evaluated at Cleveland Clinic Fhx- Noncontributory Meds- Topiramate, Clonazepam, Ranitidine, Bisacodyl Allergies- NKDA Social Hx- Lives with family, autism spectrum mentation, healthy siblings (including brother) ROS- UTO but per mom only notable for constipation

External Exam* OD OS VA UTO Pupils 4→3mm No rAPD IOP Soft (tactile) EOM Spontaneous, Full CVF *Patient currently under dexmedetomidine drip for sedation, can follow some commands though, and under continuous EEG

Anterior Segment Exam PLE OD OS External/Lids Wnl Conj/Sclera White and Quiet Cornea Clear Ant Chamber Formed Iris Lens

Posterior Segment Exam Fundus OD OS Optic Nerve Pink and sharp, Discrete lacuna superior to ON Pink & Sharp, Multiple hyperpigmented lesions inferonasal to ON in bear track pattern Macula Good foveal reflex Vessels Normal caliber Normal Caliber Periphery Wnl

DFE OD OS

MRI Brain 2015 Hypoplasia of the anterior commissure and corpus callosum rostrum

Assessment Differential Diagnosis Agenesis of Corpus Callosum Aicardi Syndrome Lennox-Gastaut Syndrome Dandy-Walker Syndrome Oral facial digital syndrome Congenital Toxoplasmosis

Aicardi Syndrome Primarily found in females (hemizygous lethality in males!!) Epidemiology- Rare Disease ~1:105,000-167,000 (including males & females)

Aicardi Syndrome Clinical Pearls Female, early in life, w/ refractory infantile spasms/epilepsy or developmental delay

Aicardi Syndrome CLASSIC Triad of Features Major Features Agenesis of Corpus Callosum Chorioretinal Lacunae Infantile Spasms Major Features Coloboma of ON (often unilateral) Cortical Malformations Periventricular heterotropia Intracranial cysts Papillomas of choroid plexus Supporting Features Vertebra & costal abnormalities Microphthalmia and/or other eye abnormalities Split brain EEG Gross cerebral hemispheric asymmetry

http://webeye. ophth. uiowa. edu/eyeforum/atlas/pages/Aicardi/index http://webeye.ophth.uiowa.edu/eyeforum/atlas/pages/Aicardi/index.htm

http://www. eurorad. org/eurorad/view_figure. php http://www.eurorad.org/eurorad/view_figure.php?pubid=1922&figid=3590&nr=1&lang=en

https://www.aao.org/pediatric-center-detail/neuro-ophthalmology-aicardi-syndrome

https://radiopaedia.org/cases/aicardi-syndrome-1 http://act.downstate.edu/courseware/np2/radiohtm/radanat/mrit1a16.htm

Aicardi Syndrome Chorioretinal Lacunae (Pathognomonic finding) Different from colobomas Defined margins, poorly differentiated/absent choriocapillaris, thin but intact Bruch’s membrane, +/- retinal cysts 1/2-3x DD size Stable size and number over time Do not affect vision typically unless involving central fovea *Embryology Pearl* Abnormal eye development at 4-8 wk gestational age, similar to corpus callosum development

Management Currently no treatment for visual dysfunction Medical/Surgical management for seizures

Prognosis Limited visual prognosis, total blindness rare. More foveal involvement of lacunae, likely positive correlation with vision loss Survival highly variable Correlated with spectrum of systemic disease, including organ system dysfunction and seizures Majority of patients live into early adulthood

Takeaway Clinical Pearls Aicardi Syndrome – RARE, females, intractable seizures, young Classic triad- absent corpus callosum, chorioretinal lacunae, infantile spasms Currently no treatment, visual prognosis variable

References Aicardi J. Aicardi Syndrome: Old and New Findings. Int Pediatr. 1998; 14(1):5-8. Sutton VR, Van den Veyver IB. Aicardi Syndrome. 2006 Jun 30 [Updated 2014 Nov 6]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1381/ McMahon R, Bell R, Moore G, Ludwin S. Aicardi's Syndrome: A Clinicopathologic Study. Arch Ophthalmol. 1984; 102(2):250-3. Beres, S. Aicardi Syndrome. 2015. https://www.aao.org/pediatric-center-detail/neuro-ophthalmology-aicardi-syndrome Parag K Shah, V Narendran, and N Kalpana. Aicardi syndrome: The importance of an ophthalmologist in its diagnosis. Indian J Ophthalmol. 2009 May-Jun; 57(3): 234–236. K. K. Suk; G. A. Lalwani; T. G. Murray; D. Hess; A. M. Berrocal. Retinal Findings in Patients With Aicardi Syndrome. Investigative Ophthalmology & Visual Science April 2010, Vol.51, 2209. BSCS Pediatric Ophthalmology and Strabismus