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Background A significant clinicopathological and genetic overlap has been suggested between amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Aim To determine the overlap, we assessed the cerebral atrophy as a surrogate indicator of FTLD in ALS inpatients with post‐tracheostomy positive pressure ventilation by CT imaging analysis. Methods The extent of cerebral atrophy was quantitatively evaluated in 92 ALS patients (age: 68.3 ± 11.0 years and disease duration: 7.6 ± 4.8 years) and 42 age‐matched healthy controls (age: 60.4 ± 13.6 years) by computer‐mediated assessments of sizes of the following four areas [anterior temporal (TL), frontal lobes (FL), and inferior horn (IH) and anterior horn (AH) of the lateral ventricle] and of the corresponding intracranial fossae, to minimize individual head‐size differences. Results More than half of the ALS patients clearly exhibited the parenchymal atrophy in TL and FL regions and the ventricular dilatation in IH and AH areas, both of which exceed the age‐associated physiological changes. By clustering analysis using degrees of TL and FL atrophy and of IH and AH dilatation the ALS patients examined were grouped into five clusters resulting in the following characteristics: (i) normal to mild frontotemporal cortical atrophy (51%); (ii) mild frontotemporal lobar atrophy (FTLA) (26%); (iii) moderate FTLA (15%); (iv) severe FTLA (4%); and (v) severe temporal lobar atrophy (3%). Conclusion Half of the ALS patients after ventilation had apparent frontotemporal lobar atrophy by CT imaging, and such patients would develop FTLD.

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