Neuropathology of sporadic amyotrophic lateral sclerosis of long duration
Introduction
Sporadic amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of unknown cause in adults. The pathology of this disease is characterized by degeneration of both the upper (UMN) and lower motor neuron (LMN) systems (Hirano et al., 1969; Hughes, 1982). One of the essential components of the clinical profile is the disease duration, with complete paralysis developing over a period of months or years. The mean duration of symptoms is about 4 years; 20% of patients live for 5 years and a few live for as long as 20 years after the onset of symptoms (Mulder and Howard, 1976; Mulder, 1982; Rowland, 1995). However, the scarcity of adequate post-mortem examinations has led to uncertainty as to whether those patients whose disease duration is several months and those who live for many decades have the same disease, although the clinical patterns and results of all available laboratory tests suggest that they are similar.
Recently, we had the opportunity to perform post-mortem examinations on three patients, who had been clinically diagnosed as having sporadic ALS or progressive spinal muscular atrophy (PSMA) of long duration. Their disease durations were 10, 17 and 20 years, respectively. In order to gain further insight into long duration ALS, we performed neuropathological examinations on these patients paying special attention to changes in the LMN and UMN systems, as well as examining two non-motor neuron systems, Clarke's column and the intermediolateral nucleus of the spinal cord.
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Patients
The three patients had each been diagnosed on the basis of clinical data including muscle biopsy and electromyography results, and their progress had been followed by neurologists. None had a familial history of similar disorders. The final clinical diagnosis, age of onset, duration of illness, site of initial symptoms, tendon reflexes, Babinski sign and degree of LMN system involvement of each of these three patients are shown in Table 1. Muscle weakness, which initially developed in the legs
Results
On gross examination, no remarkable changes were found in the brains of the patients. The entire spinal cord was atrophic, and there was wasting of the anterior roots, in each patient.
Discussion
There have been several reports concerning sporadic cases of ALS of long duration. Brownell et al. (1970)described the post-mortem findings of 45 cases of ALS, of which there were two cases of long durations, of 11 and 10 years, and in both cases, neither clinical signs of pyramidal tract involvement nor loss of cortical neurons including Betz cells were present. Brownell and coworkers concluded that these two cases differed from sporadic, classical ALS cases. On the other hand, different
Acknowledgements
We express our appreciation to Mr. S. Egawa, Mr. T. Hasegawa, Ms. Y. Ota and Ms. C. Tanda for their technical assistance, and to Ms. M. Machida and Ms. M. Fujimaki for their help in preparing the manuscript. This work was supported in part by research grants for CNS Degenerative Diseases, and Aging and Health from the Ministry of Health and Welfare, Japan.
References (21)
- et al.
Adult spinal muscular athrophy. A report of four cases
J. Neurol. Sci.
(1983) - et al.
Skein-like inclusions in the anterior horn cells in motor neuron disease
J. Neurol. Sci.
(1991) - et al.
Onset, natural history and outcome in idiopathic adult motor neuron disease
J. Neurol. Sci.
(1993) - et al.
The central nervous system in motor neurone disease
J. Neurol. Neurosurg. Psychiat.
(1970) - et al.
Anterior horn cell degeneration and Bunina-type inclusions associated with dementia
Acta Neuropathol. (Berl.)
(1977) - Hirano, A., N. Malamud, L.T. Kurland and H.M. Zimmerman (1969) A review of the pathologic findings in amyotrophic...
- Hirano, A., H. Donnenfeld, S. Sasaki, I. Nakano and H. Bartfeld (1984) The fine structure of motor neurone disease. In:...
- Hughes, J.T. (1982) Pathology of amyotrophic lateral sclerosis. In: Rowland L.P. (ed.), Human Motor Neuron Diseases,...
- et al.
Amyotrophic lateral sclerosis. A clinicoanatomic study of fifty-three cases
Arch. Neurol. Psychiat.
(1953) - et al.
Ubiquitin-immunoreactive intraneuronal inclusions in amyotrophic lateral sclerosis. Morphology, distribution, and specificity
Brain
(1991)
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