Frontotemporal and motor neurone degeneration with neurofilament inclusion bodies: additional evidence for overlap between FTD and ALS

• Published in: Neuropathology and applied neurobiology Vol. 29; no. 3; pp. 239 - 253
• Main Authors: Bigio, E. H., Lipton, A. M., White III, C. L., Dickson, D. W., Hirano, A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.06.2003; Blackwell Science
• Subjects: amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - pathology; Biological and medical sciences; Brain - metabolism; Brain - pathology; Brain - ultrastructure; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dementia - classification; Dementia - metabolism; Dementia - pathology; Dementia - physiopathology; Diagnosis, Differential; frontotemporal dementia; Humans; hyaline conglomerate inclusions; Immunohistochemistry; Inclusion Bodies - pathology; Inclusion Bodies - ultrastructure; Male; Medical sciences; Microscopy, Electron; Middle Aged; motor neurone disease; Motor Neurons - pathology; Nerve Degeneration - pathology; neurofilament; Neurofilament Proteins - metabolism; Neurology; Pick disease; Pick Disease of the Brain - pathology; ribosomes; Human; Immunohistochemistry; hyaline conglomerate inclusions; Temporal lobe; Nervous system diseases; Frontal lobe; motor neurone disease; Motor neuron disease; Amyotrophic lateral sclerosis; frontotemporal dementia; Pick disease; Electron microscopy; Case study; Pathology; ribosomes; Neurofilament; Central nervous system disease; Adult; Female; Degenerative disease; Degeneration; Inclusion body; Spinal cord disease; Dementia
• ISSN: 0305-1846; 1365-2990
• DOI: 10.1046/j.1365-2990.2003.00466.x

We present the case of a patient who had clinical frontal lobe dementia without apparent motor neurone disease (MND), with pathologic findings not typical of any single currently classified frontotemporal degeneration (FTD). At autopsy, the brain had frontal and temporal atrophy with neuronal loss, gliosis, and superficial spongiosis, typical of all FTDs. There were at least three different morphologic types of intracytoplasmic neuronal inclusions in a variety of brain and brainstem regions, including the hippocampal dentate gyrus and pyramidal neurones, the neocortex (in particular, the motor cortex), basal ganglia, thalamus, subthalamic nucleus, basis pontis, and inferior olivary nuclei. Inclusions had the morphologies of Pick‐like bodies, pleomorphic inclusions, and hyaline conglomerate (HC)‐like inclusions. None of these were positive with tau immunostains. Pick‐like bodies in the dentate gyrus were labelled with ubiquitin. The pleomorphic inclusions in the neocortex and dentate gyrus and the HC‐like inclusions in the motor and parietal cortex were strongly positive with immunostains for neurofilament. We discuss the differential diagnosis and compare this case with those disorders to which it is most similar. In particular, we compare the unique neurofilament‐positive inclusions to the inclusions of FTD‐MND, to Pick bodies, and to the basophilic and HC inclusions that are occasionally seen in amytrophic lateral sclerosis (ALS). Although FTD‐MND may be found in ALS, the findings in this case may have additional implications for a link between FTD and ALS.