Forme fruste of amyotrophic lateral sclerosis with dementia: A report of five autopsy cases without dementia and with ubiquitinated intraneuronal inclusions

We clinicopathologically investigated five autopsy cases of ALS without dementia and with ubiquitinated intraneuronal inclusions. The age at onset of symptoms ranged from 52 to 81 years and the duration of the disease was from 10 months to 3 years, 3 months. All five patients initially developed lower motor neuron signs, including bulbar signs, and upper motor neuron signs were found in the middle to late clinical stages, but dementia was not observed in all five cases. Thus, the clinical diagnoses of all five patients were ALS without dementia. Neuropathological examination of all five cases revealed not only obvious degeneration of upper motor neurons with neuronal loss of Betz cells, but also lower motor neuron involvement associated with Bunina bodies. In addition, ubiquitin-immunoreactive intraneuronal inclusions in the hippocampal dentate granular cells and degeneration of the substantia nigra were observed in all five cases. Furthermore, neuronal loss with astrocytosis in the dorsomedial portion of the anterior first temporal gyrus was observed in all three cases in which this structure was examined. Neuronal loss with astrocytosis in the subiculum was found in four cases. Neuronal loss of the parahippocampal gyrus was observed in three of the five autopsy cases, and amygdala involvement was encountered in three of four cases in which this structure was investigated. Based on these clinicopathological findings and a review of the published literature, we concluded that our five cases were ALS without dementia, but with pathological hallmarks compatible with ALS with dementia. We also concluded that there is a "forme fruste" of ALS with dementia showing no overt dementia clinically.