Mutations in the Presenilin 1 (PSEN1) gene are the most common causes of familial Alzheimer’s disease. Although cognitive symptoms are most common, some patients may also display atypical clinical features including seizures, spastic paraparesis, myoclonus, and cerebellar ataxia.
We describe a patient with PSEN1 gene mutation (p.Ala431Glu) and highlight the importance of considering mutations in PSEN1 as a cause of spastic paraparesis when testing for other more common causes are negative.
A 42-year-old right-handed man presented with a 2-year history of progressive gait decline, with balance difficulty, falls, and nocturnal shaking noted by his wife. No memory or cognitive difficulties were noted, but there were several family members affected by dementia in their 50’s in his family. Pertinent neurologic findings included MRC grade 5/5 strength throughout, 3+ reflexes in the upper extremities, 4+ reflexes in the lower extremity, and a right up-going toe. Tone was increased throughout.
MRI imaging of the brain showed microhemorrhages possibly related to CAA. MRI of the cervical, and thoracic spine showed mild degenerative changes without significant spinal stenosis, cord effacement, or other abnormalities that would be explain his symptoms. EMG did not show neurogenic changes in the bulbar, cervical, thoracic, or lumbosacral myotomes. Vitamin B12 and HTLV testing were negative. A hereditary spastic paraplegia comprehensive panel was negative. Further genetic testing revealed a PSEN1 gene mutation (p.Ala431Glu).
Although Presenilin 1 gene mutations are classically associated with familial onset Alzheimer’s Disease, it is reasonable to consider testing in patients with spastic paraparesis who have an otherwise negative workup. A detailed family history may also help in the diagnosis.