Amyotrophic lateral sclerosis with ophthalmoplegia and multisystem degeneration in patients on long-term use of respirators (original) (raw)

Summary

We describe two patients with sporadic amyotrophic lateral sclerosis (ALS), who had developed progressive external ophthalmoplegia of a predominantly supranuclear type while they survived on respirators, and displayed histopathological abnormalities both typical and atypical of ALS. Patient 1 was a 43-year-old man with ALS of 5-year duration, who had initially exhibited fulminant ALS, and remained on a respirator for 4 years. Patient 2 was a 51-year-old man with ALS of 13-year duration, who remained on a respirator for 8 years. Both patients died in a “totally locked-in state”. Autopsy of both patients revealed not only histopathological abnormalities consistent with ALS, but also multisystem degeneration which involved the pontine tegmentum, substantia nigra, Clarke's dorsal nuclei and spinocerebellar tracts. In addition, Patient 2 displayed intracyto-plasmic neuronal basophilic inclusion bodies which exhibited marked immunoreactivity to anti-ubiquitin antibodies. Our case reports indicate that the longer survival which is possible through the use of respirators may make one subgroup of ALS patients prone to develop atypical clinical and neuropathological features which are not observed during the natural cours of ALS.

Access this article

Log in via an institution

Subscribe and save

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Akiyama K, Tsutsumi Y, Onoda N, Ogawa Y, Saito H, Yoshii F, Shinohara Y (1987) An autopsy case of amyotrophic lateral sclerosis associated with sensory disturbance and eye movement disorder: pathological consideration on development of multisystem degeneration of the nervous system in a patient with prolonged survival. Byori to Rinsho 5:921–928 (in Japanese with English abstract)
    Google Scholar
  2. Brownell B, Oppenheimer DR, Hughes JH (1970) The central nervous system in motor neuron disease. J Neurol Neurosurg Psychiatry 33:338–357
    Google Scholar
  3. Chou SM (1979) Pathognomy of intraneuronal inclusions in ALS. In: Japan Medical Research Foundation (ed) Amyotrophic lateral sclerosis. University of Tokyo Press, Tokyo, pp 135–176
    Google Scholar
  4. Cohen B, Caroscio J (1983) Eye movements in amyotrophic lateral sclerosis. J Neural Transm [Suppl] 19:305–315
    Google Scholar
  5. Harvey DG, Torack RM, Rosenbaum HE (1979) Amyotrophic lateral sclerosis with ophthalmoplegia: a clinicopathologic study. Arch Neurol 36:615–617
    Google Scholar
  6. Hayashi H, Kato S (1989) Total manifestations of amyotrophic lateral sclerosis: ALS in the totally locked-in state. J Neurol Sci 93:19–35
    Google Scholar
  7. Hayashi H, Kato S, Kawada T, Tsubaki T (1987) Amyotrophic lateral sclerosis: oculomotor function in patients on respirators. Neurology 37:1431–1432
    Google Scholar
  8. Hayashi H, Kato S, Kawada A (1991) Amyotrophic lateral sclerosis patients living beyond respirator failure. J Neurol Sci 105:73–78
    Google Scholar
  9. Hirano A (1991) Cytopathology of amyotrophic lateral sclerosis. Adv Neurol 56:91–101
    Google Scholar
  10. Hudson AJ (1991) Amyotrophic lateral sclerosis and its association with dementia, parkinsonism and other neurological disorders: a review. Brain 104:217–247
    Google Scholar
  11. Iwata M (1984) Clinico-pathological studies of long survival ALS cases maintained by active life-support measures: amyotrophic lateral sclerosis. Adv Exp Med Biol 209:223–225
    Google Scholar
  12. Iwata M, Hirano A (1979) Current problems in the neuropathology of amyotrophic lateral sclerosis. Prog Neuropathol 4:277–298
    Google Scholar
  13. Kato T, Katagiri T, Hirano A, Kawanami T, Sasaki H (1989) Lewy body-like hyaline inclusions in sporadic motor neuron disease are ubiquitinated. Acta Neuropathol 77:391–396
    Google Scholar
  14. Kusaka H, Matsumoto S, Imai T (1990) An adult onset of sporadic motor neuron disease with basophilic inclusions. Acta Neuropathol 80:660–665
    Google Scholar
  15. Leigh PN, Whitewell H, Garofalo O, Buller J, Swash M, Martin JE, Gallo J-M, Weller RO, Anderton BH (1991) Ubiquitin-immunoreactive intraneuronal inclusions in amyotrophic lateral sclerosis. Morphology, distribution, and specificity. Brain 114:775–788
    Google Scholar
  16. Mizusawa H, Nakamura H, Wakayama I, Yen S-H C, Hirano A (1991) Skein-like inclusions in the anterior horn cells in motor neuron disease. J Neurol Sci 105:14–21
    Article CAS PubMed Google Scholar
  17. Mizutani T, Aki M, Shiozawa R, Unakami M, Nozawa T, Yajima K, Tanabe H, Hara M (1990) Development of ophthalmoplegia in amyotrophic lateral sclerosis during long-term use of respirators. J Neurol Sci 99:311–319
    Google Scholar
  18. Mori H, Kondo J, Ihara Y (1987) Ubiquitin is a component of paired helical filaments in Alzheimer's disease. Science 235:1641–1644
    Google Scholar
  19. Munoz DG, Greene C, Perl DP, Selkoe DJ (1988) Accumulation of phophorylated neurofilaments of amyotrophic lateral sclerosis patients. J Neuropathol Exp Neurol 47:9–18
    Google Scholar
  20. Murayama S, Mori H, Ihara Y, Bouldin TW, Suzuki K, Tomonaga M (1990) Immunocytochemical and ultrastructural studies of lower motor neurons in amyotrophic lateral sclerosis. Ann Neurol 27:137–148
    Google Scholar
  21. Nakazato Y, Sasaki A, Hirata J, Ishida Y (1987) Monoclonal antibodies which recognize phosphorylated and nonphosphorylated epitopes of neurofilament protein. Biomed Res 8:369–376
    Google Scholar
  22. Sasaki S, Maruyama S (1991) Immunohistochemical and ultrastructural studies of hyaline inclusions in sporadic motor neuron disease. Acta Neuropathol 82:295–301
    Google Scholar
  23. Schiffer D, Autilio-Gambetti L, Chio A, Gambetti P, Giordana MT, Gullotta F, Migheli A, Vigliani MC (1991) Ubiquitin in motor neuron disease: study at the light and electron microscope. J Neuropathol Exp Neurol 50:463–473
    Google Scholar
  24. Steele JC, Richardson JF, Olszewski J (1964) Progressive supranuclear palsy. Arch Neurol 10:333–359
    CAS PubMed Google Scholar
  25. Tabuchi Y, Takahashi K, Tanaka J (1983) Familial amyotrophic lateral sclerosis with ophthalmoplegia. Rinshoshinkeigaku. 23:279–287 (in Japanese with English abstract)
    Google Scholar
  26. Takahata N, Yamanouchi T, Fukatsu R, Katagiri M (1976) Brain stem gliosis in a case with clinical manifestations of amyotrophic lateral sclerosis. Folia Psychiatr Neurol Jpn 30:41–48
    Google Scholar
  27. Toyokura Y (1979) Negative features in ALS. In: Japan Medical Research Foundation (ed) Amyotrophic lateral sclerosis. University of Tokyo Press, Tokyo, pp 53–58
    Google Scholar
  28. Van Bogaert L (1925) Contribution à la connaissance des troubles oculaires et vestibulaires dans a sclérose latérale amyotrophique. Rev Oto-neuro-ocul 3:263–274
    Google Scholar
  29. Zee DS, Optican LM, Cook JD, Robinson DA, Engel WK (1976) Slow saccades in spinocerebellar degeneration. Arch Neurol 33:243–251
    Google Scholar

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Nihon University School of Medicine, 30-1 Kami-machi, Ohyaguchi, Itabashi-ku, 173, Tokyo, Japan
    T. Mizutani, S. Sakamaki, N. Tsuchiya, S. Kamei, H. Kohzu & T. Takasu
  2. First Department of Pathology, Nihon University School of Medicine, 30-1 Kami-machi, Ohyaguchi, Itabashi-ku, 173, Tokyo, Japan
    R. Horiuchi
  3. Division of Neurology, Toranomon Hospital, Tokyo, Japan
    T. Mizutani, M. Ida & R. Shiozawa
  4. Okinaka Memorial Institute for Medical Research, Tokyo, Japan
    T. Mizutani, M. Ida & R. Shiozawa

Authors

  1. T. Mizutani
    You can also search for this author inPubMed Google Scholar
  2. S. Sakamaki
    You can also search for this author inPubMed Google Scholar
  3. N. Tsuchiya
    You can also search for this author inPubMed Google Scholar
  4. S. Kamei
    You can also search for this author inPubMed Google Scholar
  5. H. Kohzu
    You can also search for this author inPubMed Google Scholar
  6. R. Horiuchi
    You can also search for this author inPubMed Google Scholar
  7. M. Ida
    You can also search for this author inPubMed Google Scholar
  8. R. Shiozawa
    You can also search for this author inPubMed Google Scholar
  9. T. Takasu
    You can also search for this author inPubMed Google Scholar

Additional information

Supported by a Grant-in-Aid from the Research Committee of CNS Degenerative Diseases, the Ministry of Health and Welfare of Japan, and by a Grant from Nihon University School of Medicine, Tokyo

Rights and permissions

About this article

Cite this article

Mizutani, T., Sakamaki, S., Tsuchiya, N. et al. Amyotrophic lateral sclerosis with ophthalmoplegia and multisystem degeneration in patients on long-term use of respirators.Acta Neuropathol 84, 372–377 (1992). https://doi.org/10.1007/BF00227663

Download citation

Key words