2025 American Academy of Neurology Abstract Website

Objective:

To describe two cases of Frontotemporal dementia (FTD) and Upper motor neuron predominant amyotrophic lateral sclerosis (ALS) due to TANK-binding kinase 1 (TBK1) gene mutation.

Background:

Mutation in the TBK 1 gene can cause ALS and FTD.

Design/Methods:

Case Series.

Results:

Patient 1, a 76-year-old female, presented for evaluation of progressive painless weakness of 2-year duration that started in bilateral lower extremities followed by right upper extremity, then left upper extremity, and eventually progressive bulbar weakness and pseudobulbar affect. Examination showed bilateral lower and right upper extremity and proximal>distal left upper extremity weakness with numerous upper motor neuron (UMN) and lower motor neuron (LMN) signs. Her father and grandfather were both diagnosed with ALS. Electromyography (EMG) showed large fiberneuropathy but no active and chronic denervation changes to suggest lower motor neuronopathy. Magnetic resonance imaging (MRI) of brain showed temporal>frontal atrophy. Genetic testing returned positive for TBK1 mutation.

Patient 2, a 66-year-old male presented with progressive, asymmetric, painless motor weakness of 2-year duration that started in the left upper and lower extremities followed by change in personality, memory difficulties, bulbar weakness and eventually distal right lower extremity weakness. Examination notable for distal> proximal, left> right lower extremity and left upper extremity weakness with numerous UMN and LMN signs. His father and sister were diagnosed with ALS. EMG showed large fiber neuropathy with chronic denervation changes in distal upper and lower extremities. There was no evidence of active denervation to suggest lower motor neuronopathy. Genetic testing returned positive for TBK1 mutation. MRI brain showed atrophy in frontal and temporal regions. Patient was diagnosed with frontotemporal dementia (FTD) – ALS syndrome.

Conclusions:

Our study highlights unique presentation of FTD-ALS associated with TBK1 gene mutation where despite clinical signs of lower motor neuron involvement including weakness, atrophy, and fasciculations, the electromyography did not indicate lower motor neuronopathy.