Abstract Details

Title Perampanel associated with developmental regression in patient with FRRS1L mutation

Topic Child Neurology and Developmental Neurology

Presentation(s) P14 - Poster Session 14 (8:00 AM-9:00 AM)

Poster/Presentation
Number 5-011

Objective To describe a case of developmental regression concurrent with perampanel initiation in a patient with FRRS1L mutation

Background AMPA-type glutamate receptors are key elements of excitatory neurotransmission in the brain. The receptors’ highly variable functions derive from the diverse assembly of their proteome. FRRS1L is primarily restricted to the endoplasmic reticulum where it forms a complex with CPT-1C and Sac1 for early AMPAR assembly prior to translocation to the plasma membrane. Perampanel, a novel antiepileptic, is a selective noncompetitive AMPA receptor agonist.

Design/Methods Descriptive case report

Results 3 year old Kuwaiti female, product of consanguineous marriage, initially presented with seizures at age 2.5 consisting of arrest of activity, upward eye rolling, limpness, and unresponsiveness. Medication trials with valproic acid, cortisone, levetericetam, and lacosamide failed to control seizures. Two days after initiation of perampanel, patient was noted to have motor and speech regression. Patient had been able to stand unassisted and walk short distances but developed acute onset imbalance, head drop, and overall slowed movements on perampanel initiation. Patient eventually stopped ambulating and was unable to sit unassisted. As perampanel was weaned, patient regained some function such as sitting but continued to have poor head control and remained non-ambulatory. Speech also regressed from more than 10 to 5-6 words with stabilization after perampanel discontinuation. EEG on a regimen of valproic acid, lacosamide, and vigabatrin showed generalized spike and wave complexes both in awake and sleep. MRI brain was normal. Exome sequencing showed homozygous c.578G>A p.(Gly193Asp) missense mutation in the FRRS1L gene and heterozygous c2771C>T p.(Ser924Phe) missense mutation in the ASH1L gene.

Conclusions We present a case of novel mutation in FRRS1L associated with epilepsy and hypotonia in which developmental regression was associated with initiation of perampanel. Further research is needed to understand the effects of perampanel on this type of AMPA receptor mutations.

Authors/Disclosures
Chen Yan, MD (Cleveland Clinic) PRESENTER	Dr. Yan has nothing to disclose.
Hussam Shaker, MD (C&RMEP)	Dr. Shaker has nothing to disclose.
	No disclosure on file
Prakash Kotagal, MD, MBBS, F�鶹��ýӳ�� (Cleveland Clinic Foundation)	No disclosure on file
Ajay Gupta, MD (Head, Pediatric Epilepsy, Cleveland Clinic Foundation)	Dr. Gupta has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurelis. Dr. Gupta has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GW Pharma.

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