Evidence for pathological involvement of the spinal cord in motor neuron disease-inclusion dementia

Fronto-temporal dementia (FTD), characterised pathologically by ubiquitinated inclusions in the hippocampal dentate fascia and fronto-temporal cortex, may develop in association with motor neuron disease (MND). However, FTD with identical pathological hallmarks may occur in isolation and has been termed motor neuron disease-inclusion dementia (MND-ID). We studied the pathology of three cases of MND-ID including the spinal cord, which has not previously been examined in this condition. The ages of the patients at death were 53, 70 and 68 years and the onset of FTD 10, 15 and 9 years before death. Neuropathological findings in all cases included micro-vacuolation in cortical layer II and ubiquitinated intraneuronal inclusions in fronto-temporal cortex and hippocampal dentate fascia. One case showed unusual basophilic, ubiquitinated neuronal cytoplasmic inclusions in the brain stem. Qualitative assessment of the spinal cord was normal in two cases, while the third showed mild pallor of the lateral cortico-spinal tracts and ubiquitinated inclusions in motor neurons typical of MND. Morphometry did not reveal any significant loss or decrease in size of anterior horn motor neurons. The results of this study are consistent with the hypothesis that the pathological changes of pure MND and MND-ID form a spectrum and demonstrate that pathological involvement of the motor system may occur in MND-ID without clinical evidence of MND.