Unexpected postmortem diagnoses in cases of clinically diagnosed amyotrophic lateral sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is a motor neuron disease that is clinically and pathologically characterized by impairment of the upper and lower motor neurons. The clinical diagnosis of ALS is not always straightforward because of the lack of specific biomarkers and clinical heterogeneity. This review presents the clinical and pathological findings of four autopsied cases that had been diagnosed with ALS before death. These cases had demonstrated definite and progressive motor neuron signs and symptoms, whereas postmortem assessment revealed miscellaneous disorders, including fungal infection, paraneoplastic syndrome, and amyloidosis. Importantly, nonmotor neuron signs and symptoms, including seizures, extra-pyramidal signs, ocular movement disorders, sensory disturbance, and dysautonomia, had also been documented during the disease course of the cases in the present study. The ALS-unlike symptoms were indicative of the "true" diagnosis in each case when those symptoms were isolated from motor neuron signs/ symptoms.

Autonomic dysfunction in amyotrophic lateral sclerosis: A neurophysiological and neurosonology study

“…4 A subset of ALS patients, defined as ALS-Plus, 5 exhibits other nonmotor signs, extrapyramidal or autonomic, that may be clinical or subclinical, the latter usually revealed on pathological postmortem grounds. 6 Based on the above, ALS can be considered a multisystem degenerative disease. [7][8][9][10] Regarding autonomous nervous system (ANS) involvement, several researchers have investigated heart rate variability (HRV) as a measure of dysautonomia in ALS patients.…”

“…It is estimated that half of patents with ALS experience cognitive or behavioral impairment, 3 a percentage of whom develop frontotemporal dementia 4 . A subset of ALS patients, defined as ALS‐Plus, 5 exhibits other nonmotor signs, extrapyramidal or autonomic, that may be clinical or subclinical, the latter usually revealed on pathological postmortem grounds 6 . Based on the above, ALS can be considered a multisystem degenerative disease 7–10 …”

Neuropathology Case Cluster: Neuropathology of focal cortical, behavioral, and psychiatric syndromes in neurodegenerative diseases (neuropathology cluster case 14–32)

“…The authors disclose no conflict of interest. Shinobu Kawakatsu, 1 Toshiki Uchihara, 2,3,4 Masaki Takao 5 and Noriyuki Shibata…”

“…Traditionally, in Japan, dedicated psychiatrists and neurologists have made great efforts to evaluate the heterogeneity of these neuropsychiatric symptoms neuropathologically as well as neuropsychologically. Herein, neurodegenerative diseases with primary progressive aphasia or late‐onset psychosis that have recently attracted attention in clinical settings are presented as sequels to the Neuropathological Case Cluster ( NCC ), inaugurated in Neuropathology 1–5 . NCC will increase the significance of case reports by contrasting multiple cases and encourage many researchers to report case series.…”

“…Herein, neurodegenerative diseases with primary progressive aphasia or late-onset psychosis that have recently attracted attention in clinical settings are presented as sequels to the Neuropathological Case Cluster (NCC), inaugurated in Neuropathology. [1][2][3][4][5] NCC will increase the significance of case reports by contrasting multiple cases and encourage many researchers to report case series.…”