Skip to main content
SpringerLink
Log in

Brainstem in Multiple System Atrophy: Clinicopathological Correlations

  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Abstract

1. Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder that manifests with parkinsonism, cerebellar ataxia, and autonomic failure in various combinations.

2. Orthostatic hypotension, neurogenic bladder, laryngeal stridor and sleep apnea, and rapid eye movement (REM) sleep behavior disorder are prominent manifestations of MSA.

3. In MSA, there is severe depletion of catecholaminergic neurons of the C1 and A1 areas in the ventrolateral medulla, and this may contribute to orthostatic hypotension and endocrine disturbances in this disorder, respectively.

4. Loss of corticotrophin-releasing factor (CRF) neurons in the pontine micturition area may contribute to neurogenic bladder dysfunction.

5. Respiratory abnormalities may reflect loss of cholinergic neurons in the arcuate nucleus of the ventral medulla.

6. Loss of cholinergic mesopontine neurons, in the setting of loss of locus ceruleus neurons and preservation of rostral raphe neurons, may contribute to REM sleep abnormalities in MSA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  • Bannister, R. (1993). Multiple system atrophy and pure autonomic failure. In Low, P. A. (ed.), Clinical Autonomic Disorders: Evaluation and Management, Little, Brown, Boston, pp. 517–526.

    Google Scholar 

  • Bannister, R., Gibson, W., Michaels, L., and Oppenheimer, D. R. (1981). Laryngeal abductor paralysis in multiple system atrophy. A report on three necropsied cases, with observations on the laryngeal muscles and the nucleus ambiguus. Brain 104:351–368.

    PubMed  Google Scholar 

  • Benarroch, E. E., Schmeichel, A. M., and Parisi, J. E. (2000). Involvement of the ventrolaterol medulla in Parkinsonism with autonomic failure. Neurology 54:963–968.

    PubMed  Google Scholar 

  • Benarroch, E. E., and Schmeichel, A. M. (2001). Depletion of corticotrophin-releasing factor neurons in the pontine micturition area in multiple system atrophy. Ann. Neurol. 50:640–645.

    PubMed  Google Scholar 

  • Benarroch, E. E., Schmeichel, A. M., and Parisi, J. E. (2001). Depletion of cholinergic neurons of the medullary arcuate nucleus in multiple system atrophy. Auton. Neurosci. 87:293–299.

    PubMed  Google Scholar 

  • Benarroch, E. E., Schmeichel, A. M., and Parisi, J. E. (2002). Depletion of mesopontine cholinergic and sparing of raphe neurons in multiple system atrophy. Neurology 59:944–946.

    PubMed  Google Scholar 

  • Benarroch, E. E., Smithson, I. L., Low, P. A., and Parisi, J. E. (1998). Depletion of catecholaminergic neurons of the rostral ventrolateral medulla in multiple systems atrophy with autonomic failure. Ann. Neurol. 43:156–163.

    PubMed  Google Scholar 

  • Blessing, W. W. (1997). The Lower Brainstem and Bodily Homeostasis, Oxford University Press, New York.

    Google Scholar 

  • Blessing, W. W., and Willoughby, J. O. (1987). Central neural pathways mediating baroreceptor-initiated secretion of vasopressin. In Hainsworth, R., McWilliam, P. N., and Mary Das (eds.), Cardiogenic Reflexes, Oxford University Press, Oxford, pp. 301–317.

    Google Scholar 

  • Chandiramani, V. A., and Fowler, C. J. (1999). Urogenital disorders in Parkinson's disease and multiple system atrophy. In Fowler, C. J. (ed.), Neurology of Bladder, Bowel, and Sexual Dysfunction, Butterworth-Heinemann, Boston, pp. 245–254.

    Google Scholar 

  • Chokroverty, S. (1988). Sleep apnoea and respiratory disturbances in multiple system atrophy with autonomic failure. In Bannister, R. (ed.), Autonomic Failure, Oxford Medical Publications, Oxford, pp. 432–450.

    Google Scholar 

  • Day, T. A., and Sibbald, J. R. (1989). A1 cell group mediates solitary nucleus excitation of supraoptic vasopressin cells. Am. J. Physiol. 257:R1020-R1026.

    PubMed  Google Scholar 

  • Filiano, J. J., Choi, J. C., and Kinney, H. C. (1990). Candidate cell populations for respiratory chemosensitive fields in the human infant medulla. J. Comp. Neurol. 293:448–465.

    PubMed  Google Scholar 

  • Gai, W. P., Geffen, L. B., Denoroy, L., and Blessing, W. W. (1993). Loss of C1 and C3 epinephrine-synthesizing neurons in the medulla oblongata in Parkinson's disease. Ann. Neurol. 33:357–367.

    PubMed  Google Scholar 

  • Gilman, S., Low, P. A., Quinn, N., Albanese, A., Ben-Shlomo, Y., Fowler, C. J., Kaufmann, H., Klockgether, T., Lang, A. E., Lantos, P. L., Litvan, I., Mathias, C. J., Oliver, E., Robertson, D., Schatz, I., and Wenning, G. K. (1999). Consensus statement on the diagnosis of multiple system atrophy. J. Neurol. Sci. 163:94–98.

    PubMed  Google Scholar 

  • Goldstein, D. S., Holmes, C., Cannon, R. O., III, Eisenhofer, G., and Kopin, I. J. (1997). Sympathetic cardioneuropathy in dysautonomias. N. Engl. J. Med. 336:696–702.

    PubMed  Google Scholar 

  • Gozal, D., Hathout, G. M., Kirlew, K. A. T., Tang, H., Woo, M. S., Zhang, J., Lufkin, R. B., and Harper, R. M. (1994). Localization of putative neural respiratory regions in the human by functional magnetic resonance imaging. J. Appl. Physiol. 76:2076–2083.

    PubMed  Google Scholar 

  • Guyenet, P. G., Koshiya, N., Huangfu, D., Baraban, S. C., Stornetta, R. L., and Li, Y. W. (1996). Role of medulla oblongata in generation of sympathetic and vagal outflows. Prog. Brain Res. 107:127–144.

    PubMed  Google Scholar 

  • Halliday, G. M., Blumbergs, P. C., Cotton, R. G., Blessing, W. W., and Geffen, L. B. (1990). Loss of brainstem serotonin-and substance P-containing neurons in Parkinson's disease. Brain Res. 510:104–107.

    PubMed  Google Scholar 

  • Hobson, J. A. (1992). Sleep and dreaming: Induction and mediation of REM sleep by cholinergic mechanisms. Curr. Opin. Neurobiol. 2:759–763.

    PubMed  Google Scholar 

  • Holstege, G., Griffiths, D., de Wall, H., and Dalm, E. (1986). Anatomical and physiological observations on supraspinal control of bladder and urethral sphincter muscles in the cat. J. Comp. Neurol. 250:449–461.

    PubMed  Google Scholar 

  • Iadecola, C., Faris, P. L., Hartman, B. K., and Xu, X. (1993). Localization of NADPH diaphorase in neurons of the rostral ventral medulla: Possible role of nitric oxide in central autonomic regulation and oxygen chemoreception. Brain Res. 603:173–179.

    PubMed  Google Scholar 

  • Isono, S., Shiba, K., Yamaguchi, M., Tanaka, A., Hattori, T., Konno, A., and Nishino, T. (2001). Pathogenesis of laryngeal narrowing in patients with multiple system atrophy. J. Physiol. 536:237–249.

    PubMed  Google Scholar 

  • Isozaki, E., Matsubara, S., Hayashida, T., Oda, M., and Hirai, S. (2000). Morphometric study of nucleus ambiguus in multiple system atrophy presenting with vocal cord abductor paralysis. Clin. Neuropathol. 19:213–220.

    PubMed  Google Scholar 

  • Jellinger, K. A., and Paulus, W. (1992). Clinico-pathological correlations in Parkinson's disease. Clin. Neurol. Neurosurg. 94:S86-S88.

    PubMed  Google Scholar 

  • Kaufmann, H., Oribe, E., Miller, M., Knott, P., Wiltshire Clement, M., and Yahr, M. D. (1992). Hypotension-induced vasopressin release distinguishes between pure autonomic failure and multiple system atrophy with autonomic failure. Neurology 42:590–593.

    PubMed  Google Scholar 

  • Kinney, H. C., Filiano, J. J., Sleeper, L. A., Mandell, F., Valdes-Dapena, M., and White, W. F. (1995). Decreased muscarinic receptor binding in the arcuate nucleus in sudden infant death syndrome. Science 269:1446–1450.

    PubMed  Google Scholar 

  • Lantos, P. L. (1998). The definition of multiple system atrophy: A review of recent developments. J. Neuropathol. Exp. Neurol. 57:1099–1111.

    PubMed  Google Scholar 

  • Loewy, A. D., and Spyer, K. M. (1990). Vagal preganglionic neurons. In Loewy, A. D., and Spyer, K. M. (eds.), Central Regulation of Autonomic Functions, Oxford University Press, New York, pp. 68–87.

    Google Scholar 

  • Merlo, I. M., Occhini, A., Pacchetti, C., and Alfonsi, E. (2002). Not paralysis, but dystonia causes stridor in multiple system atrophy. Neurology 58:649–652.

    PubMed  Google Scholar 

  • Noda, K., Katayama, S., Watanabe, C., Yamamura, Y., and Nakamura, S. (1997). Decrease of neurons in the medullary arcuate nucleus of multiple system atrophy: Quantitative comparison with Parkinson's disease and amyotrophic lateral sclerosis. J. Neurol. Sci. 151:89–91.

    PubMed  Google Scholar 

  • Oppenheimer, D. R. (1980). Lateral horn cells in progressive autonomic failure. J. Neurol. Sci. 46:393–404.

    PubMed  Google Scholar 

  • Papp, M. I., Kahn, J. E., and Lantos, P. L. (1989). Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy–Drager syndrome). J. Neurol. Sci. 94:79–100.

    PubMed  Google Scholar 

  • Plazzi, G., Cortelli, P., Montagna, P., De Monte, A., Corsini, R., Contin, M., Provini, F., Pierangeli, G., and Lugaresi, E. (1998). REM sleep behaviour disorder differentiates pure autonomic failure from multiple system atrophy with autonomic failure. J. Neurol. Neurosurg. Psychiatry 64:683–685.

    PubMed  Google Scholar 

  • Puritz, R., Lightman, S. L., Wilcox, C. S., Forsling, M., and Bannister, R. (1983). Blood pressure and vasopressin in progressive autonomic failure. Response to postural stimulation, L-dopa and naloxone. Brain 106:503–511.

    PubMed  Google Scholar 

  • Sakai, K., Crochet, S., and Onoe, H. (2001). Pontine structures and mechanisms involved in the generation of paradoxical (REM) sleep. Arch. Ital. Biol. 139:93–107.

    PubMed  Google Scholar 

  • Saper, C. B., Sorrentino, D. M., German, D. C., and de Lacalle, S. (1991). Medullary catecholaminergic neurons in the normal human brain and in Parkinson's disease. Ann. Neurol. 29:577–584.

    PubMed  Google Scholar 

  • Smith, J. C., Ellenberger, H. H., Ballanyi, K., Richter, D. W., and Feldman, J. L. (1991). Pre-Bötzinger complex: A brainstem region that may generate respiratory rhythm in mammals. Science 254:726–729.

    PubMed  Google Scholar 

  • Spyer, K. M. (1994). Annual Review Prize Lecture: Central nervous mechanisms contributing to cardiovascular control. J. Physiol. 474:1–19.

    PubMed  Google Scholar 

  • Thomaides, T., Bleasdale-Barr, K., Chaudhuri, K. R., Pavitt, D., Marsden, C. D., and Mathias, C. J. (1993). Cardiovascular and hormonal responses to liquid food challenge in idiopathic Parkinson's disease, multiple system atrophy, and pure autonomic failure. Neurology 43:1181–1187.

    PubMed  Google Scholar 

  • Valentino, R. J., Pavcovich, L. A., and Hirata, H. (1995). Evidence for corticotropin-releasing hormone projections from Barrington's nucleus to the periaqueductal gray and dorsal motor nucleus of the vagus in the rat. J. Comp. Neurol. 363:402–422.

    PubMed  Google Scholar 

  • Wang, H., Stornetta, R. L., Rosin, D. L., and Guyenet, P. G. (2001). Neurokinin-1 receptor-immunoreactive neurons of the ventral respiratory group in the rat. J. Comp. Neurol. 434:128–146.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA

    Eduardo E. Benarroch

Authors
  1. Eduardo E. Benarroch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eduardo E. Benarroch.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Benarroch, E.E. Brainstem in Multiple System Atrophy: Clinicopathological Correlations. Cell Mol Neurobiol 23, 519–526 (2003). https://doi.org/10.1023/A:1025067912199

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1025067912199

Search

Navigation