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Abstract Details

Concurrent Alzheimer disease and primary lateral sclerosis associated with presenilin-1 gene mutation in a 30-year-old man
Aging, Dementia, and Behavioral Neurology
P8 - Poster Session 8 (8:00 AM-9:00 AM)
10-008

To present a rare case of concurrent early onset familial Alzheimer disease (EOFAD) and primary lateral sclerosis (PLS) in the setting of a presenilin 1 (PSEN1) missense mutation (p. Leu381Phe)

Genetic linkage analysis studies of EOFAD have demonstrated that most cases are associated with autosomal dominant mutations in the APP, PSEN1, and PSEN2 genes, with >50% being associated with PSEN1 mutations. There have been over 200 pathogenic PSEN1 gene mutations reported to date with high variability in phenotypic expression, including associated spastic paraparesis. However, only one case report to date has discussed the distinct diagnosis of PLS associated with a PSEN1 mutation.
Case report and literature review
A 30-year-old man presented to clinic with a one-year history of bilateral lower extremity weakness, dysarthria, gait disturbance, and memory loss. The initial exam revealed spastic dysarthria, proximal lower extremity weakness and spasticity, and upper motor neuron signs in all extremities. Initial studies included magnetic resonance imaging of the brain and spinal cord, electromyography, antibody testing, paraneoplastic panel, a lumbar puncture, all of which were unremarkable. Genetic testing was sent for familial motor neuron disease, which revealed a previously reported pathogenic mutation in PSEN1. With pure upper motor neuron involvement in three body regions, the patient was given a diagnosis of PLS. He was also assessed for his memory complaints and determined to have either mild cognitive impairment or early dementia, also likely due to the PSEN1 mutation.
This case demonstrates a rare concurrence of two seemingly distinct neuropathologic processes in the setting of a pathogenic mutation in the PSEN1 gene. While there have been reports of phenotypic overlay of lower extremity spasticity in the setting of EOFAD due to PSEN1 mutations, our case suggests that the overlap with motor neuron disease is more extensive than previously thought.
Authors/Disclosures
Erica E. Lewis, DO (Cedars-Sinai)
PRESENTER 		No disclosure on file
Glen R. Finney, MD, FÂ鶹´«Ã½Ó³»­ (Geisinger Health) Dr. Finney has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Premier Inc. Dr. Finney has a non-compensated relationship as a Board Member with Greater Pennsylvania Chapter of the Alzheimer's Association that is relevant to Â鶹´«Ã½Ó³»­ interests or activities.
J. David Avila, MD, FÂ鶹´«Ã½Ó³»­ (Geisinger Medical Center) Dr. Avila has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AstraZeneca. Dr. Avila has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Alnylam Pharmaceuticals. Dr. Avila has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for argenx. Dr. Avila has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion Pharmaceuticals. Dr. Avila has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for UCB. Dr. Avila has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for AstraZeneca. Dr. Avila has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Takeda.