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)
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Location of Involvement
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Syndrome
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Pathology
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upper motor neuron
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pseudobulbar palsy
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corticospinal tracts
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lower motor neuron
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bulbar palsy
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anterior horn cells, motor nuclei of the cranial nerves
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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
