A patient with a motor neuron disease (MND) may develop a dementia which has clinical and pathologic features of frontotemporal lobe dementia (FTLD).


Designation: FTLD-MND


Motor neuron disease (MND) is a heterogenous group of disorders with:

(1) loss of upper motor neurons (with degeneration in the corticospinal tracts) and/or

(2) loss of lower motor neurons (involving the motor neurons of the cranial nerves and anterior horn cells of the spinal cord)


Examples of MND: amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS)

Location of Involvement



upper motor neuron

pseudobulbar palsy

corticospinal tracts

lower motor neuron

bulbar palsy

anterior horn cells, motor nuclei of the cranial nerves


Patients with motor neuron disease often have emotional lability and a mild cognitive impairment. A small subset of patients may develop clinical dementia.


Features of the dementia:

(1) insidious onset

(2) progressive

(3) prominent behavioral and/or language dysfunction

(4) impaired memory for visual and verbal material

(5) occasional rapidly progressive aphasic dementia


A brain biopsy shows inclusions within neuorons (primarily motor neurons) that are tau negative, alpha-synuclein negative and ubiquitin positive. According to Neumann et al (2006), the inclusions are composed of ubiquinated TDP-43, the protein product of the TARDP gene on chromosome 1.


Location of inclusions:

(1) substantia nigra

(2) hippocampus

(3) neocortex

(4) spinal cord


Pathologic features of FTLD are seen in the frontotemporal neocortex:

(1) superficial spongiosis

(2) neuronal loss (primarily in layer II)

(3) astrogliosis


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