The Japanese journal of neuropsychology

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ArticleTitle	ALS and distribution of its pathology
Language	J
AuthorList	Imaharu Nakano
Affiliation	Division of Neurology, Department of Internal Medicine, Jichi Medical University School of Medicine
Publication	Japanese Journal of Neuropsychology: 28 (3), 191-198, 2012
Received
Accepted
Abstract	Our common concept on ALS is that it is a rather homogeneous condition characterized clinically with sporadic onset after middle age, and relentless lethal progress, and pathologically with loss of the upper and lower motor neurons and appearance of Bunina bodies and TDP-43 inclusions. The homogeneity has not been proven, however. Rather, recent studies, especially molecular genetics, seem to show heterogeneity of this condition. ALS is a disease concept defined topographically by degeneration of the upper and lower motor neurons and chronologically by its progress. Therefore, ALS comes to inevitably include heterogenous diseases that fulfill the above-mentioned conditions irrespective of the underlying pathomechanisms. A proportion of ALS patients with TDP-43 deposition show characteristic dementia that is probably associated with the cerebral cortical degeneration of the frontal and temporal lobes. This condition is named as ALS with dementia (ALSD) or frontotemporal degeneration-motor neuron disease (FTLD-MND), in which neurons and glial cells in the wide-spread regions of the brain contain TDP-43 inclusion bodies and nigral pigmented neurons are degenerated without Lewy body appearance. In addition, in ALSD, there is unique degeneration of the pyramidal cells confined to the transitional zone between the hippocampal CA1 and subiculum, and early degeneration of the superficial layer neurons of the medical cortex at the temporal poles. In this condition, Exner's area, which is located at the posterior region of the left middle frontal lobe gyrus and is related to letter-spelling process may also undergo degeneration. Thus, recent advances in the molecular pathology have confirmed that the cerebral lesion in ALS is much wider than considered previously.
Keywords	amyotrophic lateral sclerosis, amyotrophic lateral sclerosis with dementia, neuropathology, pathology distribution, frontotemporal lobar degeneration