Case 27-2004: Multiple-System Atrophy
http://www.100md.com
《新英格兰医药杂志》
To the Editor: In reviewing the differential diagnosis in the case of a woman with disturbances in gait, cognition, and autonomic function, Schlossmacher provides a scholarly discussion of multiple-system atrophy (Aug. 26 issue),1 but he errs by including pure autonomic failure as one of four syndromes subsumed under the diagnosis of multiple-system atrophy.
Pure autonomic failure is a distinct and separate clinical entity that affects postganglionic neurons. Autonomic impairment is the principal manifestation; orthostatic hypotension, bladder incontinence, and impotence in men are the major signs.2 Pure autonomic failure differs importantly from multiple-system atrophy in its lack of any sensory, cerebellar, pyramidal, or extrapyramidal dysfunction. Afferent pathways and somatic neurons are not affected. It is strikingly less progressive than multiple-system atrophy, and patients usually have a prolonged and sometimes stable course.
This distinction is important, because it helps clinicians separate several puzzling and sometimes overlapping neurodegenerative disorders.3,4
Irwin J. Schatz, M.D.
University of Hawaii John A. Burns School of Medicine
Honolulu, HI 96813
schatzi@hawaii.edu
References
Case Records of the Massachusetts General Hospital (Case 27-2004). N Engl J Med 2004;351:912-922.
Robertson D, ed. Primer on the autonomic nervous system. 2nd ed. New York: Elsevier Academic Press, 2004:309.
Schatz I. Farewell to the "Shy-Drager syndrome." Ann Intern Med 1996;125:74-75.
Kaufman H. Consensus statement on the definition of orthostatic hypotension, pure autonomic failure and multiple system atrophy. Clin Auton Res 1996;6:125-126.
To the Editor: The clinicopathological report about a 79-year-old woman with gait, cognition, and autonomic disturbances centered on differential diagnostic features of multiple-system atrophy. Most patients with multiple-system atrophy have orthostatic hypotension. Indeed, the report by Shy and Drager1 that led to the eponym the Shy–Drager syndrome was entitled, "A Neurological Syndrome Associated with Orthostatic Hypotension." The term "multiple-system atrophy" replaced the eponym in the mid-1990s.2 The case presentation should have noted whether the patient had normal or abnormal orthostatic blood pressure instead of mentioning only that "her vital signs were normal." Moreover, because of poor baroreflex function associated with multiple-system atrophy,3 the patient may have also had a constant pulse rate despite having orthostatic hypotension — another abnormal and pertinent finding. In regard to the use of laboratory testing to distinguish multiple-system atrophy from Parkinson's disease, more than 20 studies worldwide have shown that Parkinson's disease entails decreased or absent cardiac sympathetic innervation, whereas multiple-system atrophy does not; this finding may prove important not only for differential diagnosis,4 but also for understanding the pathogenetic mechanisms of the two diseases.
David S. Goldstein, M.D., Ph.D.
National Institute of Neurological Disorders and Stroke
Bethesda, MD 20892-1620
goldsteind@ninds.nih.gov
References
Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension: a clinical-pathological study. Arch Neurol 1960;2:511-527.
Schatz I. Farewell to the "Shy-Drager syndrome." Ann Intern Med 1996;125:74-75.
Goldstein DS, Pechnik S, Holmes C, Eldadah B, Sharabi Y. Association between supine hypertension and orthostatic hypotension in autonomic failure. Hypertension 2003;42:136-142.
Braune S. The role of cardiac metaiodobenzylguanidine uptake in the differential diagnosis of parkinsonian syndromes. Clin Auton Res 2001;11:351-355.
To the Editor: In the discussion of management in the August 26 Case Record, Dr. Hamann does not say how long the patient survived after she met the criteria for enrollment in hospice. If the doctors associated with the patient's hospice predicted that she had less than six months to live at four years, three years, two years, and one year before her actual death, then these differences between prediction and observation are part of the data of Dr. Hamann's case and should be reported. In a similar fashion, the sources of the (incorrect) prognoses should be cited and discussed. A 1999 study1 that used criteria from the National Hospice Organization's "Medical Guidelines for Determining Prognosis in Selected Non-Cancer Diseases"2 found that hospice criteria were not accurate in predicting survival in a group of 2600 patients with advanced chronic obstructive pulmonary disease, congestive heart failure, or liver disease; in a subgroup that was predicted to have less than a 10 percent chance of living for six months, 41 percent survived for more than six months.
Richard A. Martin, M.D.
9448 W. Edgar Earl Loop
Crystal River, FL 34428
References
Fox E, Landrum-McNiff K, Zhong Z, Dawson NV, Wu AW, Lynn J. Evaluation of prognostic criteria for determining hospice eligibility in patients with advanced lung, heart, or liver disease. JAMA 1999;282:1638-1645.
Stuart B, Alexander C, Arenella C, et al. Medical guidelines for determining prognosis in selected non-cancer diseases. 2nd ed. Alexandria, Va.: National Hospice and Palliative Care Organization, 1996.
The authors reply: Dr. Goldstein inquires about orthostasis in our patient, mentions testing of cardiac innervation for diagnostic accuracy, and raises the issue of pathogenesis. During the first three years of our patient's illness, there were no detectable abnormalities in blood pressure or heart rate, but she declined to undergo formal autonomic testing. During the final year of her life, postural dizziness was observed with passive transfers, but orthostasis was not recorded.
Reports of a loss of sympathetic cardiac innervation in Parkinson's disease relied on detection by radioligands, such as 6-[18F]fluorodopamine.1 Progressive dysinnervation was found in sporadic cases and in familial forms of the disease with mutations in the -synuclein gene. These studies suggested that degeneration of peripheral, postganglionic sympathetic neurons in Parkinson's disease was a result of abnormal -synuclein metabolism.1 In contrast, autonomic dysfunction in multiple-system atrophy arises chiefly from degeneration in the central nervous system and of preganglionic cells,2 although -synuclein deposits have been described in peripheral gangliocytes in a few cases. We concur with Dr. Goldstein that the distinction between multiple-system atrophy and Parkinson's disease with dysautonomia has been improved by monoaminergic radiolabeling studies.3
Dr. Schatz identifies an editing error by Dr. Schlossmacher, who misused the word "pure" in characterizing autonomic failure in multiple-system atrophy (the Shy–Drager syndrome). As a disease of the peripheral nervous system, pure autonomic failure lacks involvement of the central nervous system and, thus, signs of parkinsonism or cerebellar dysfunction. Adding to the complexities in nomenclature and pathophysiology, pure autonomic failure shares with Parkinson's disease the predilection for postganglionic neurons and the characteristic, intraneuronal accumulation of -synuclein.4
Dr. Martin asks whether our patient exemplified the known inaccuracy of predicting death within six months of hospice enrollment. During the last six months of her life, she resided in a nursing home that provided full palliative care and did not need a hospice referral. In general, we favor a hospice approach for patients with advanced neurodegenerative diseases.5
Michael G. Schlossmacher, M.D.
Claus Hamann, M.D.
Harvard Medical School
Boston, MA 02115
mschlossmacher@rics.bwh.harvard.edu
References
Singleton A, Gwinn-Hardy K, Sharabi Y, et al. Association between cardiac denervation and parkinsonism caused by alpha-synuclein gene triplication. Brain 2004;127:768-772.
Benarroch EE, Schmeichel AM, Low PA, Parisi JE. Involvement of medullary serotonergic groups in multiple system atrophy. Ann Neurol 2004;55:418-422.
Riley DE, Chelimsky TC. Autonomic nervous system testing may not distinguish multiple system atrophy from Parkinson's disease. J Neurol Neurosurg Psychiatry 2003;74:56-60.
Arai K, Kato N, Kashiwado K, Hattori T. Pure autonomic failure in association with human alpha-synucleinopathy. Neurosci Lett 2000;296:171-173.
Volicer L, Hurley A. Hospice care for patients with advanced progressive dementia. New York: Springer, 1998.
Pure autonomic failure is a distinct and separate clinical entity that affects postganglionic neurons. Autonomic impairment is the principal manifestation; orthostatic hypotension, bladder incontinence, and impotence in men are the major signs.2 Pure autonomic failure differs importantly from multiple-system atrophy in its lack of any sensory, cerebellar, pyramidal, or extrapyramidal dysfunction. Afferent pathways and somatic neurons are not affected. It is strikingly less progressive than multiple-system atrophy, and patients usually have a prolonged and sometimes stable course.
This distinction is important, because it helps clinicians separate several puzzling and sometimes overlapping neurodegenerative disorders.3,4
Irwin J. Schatz, M.D.
University of Hawaii John A. Burns School of Medicine
Honolulu, HI 96813
schatzi@hawaii.edu
References
Case Records of the Massachusetts General Hospital (Case 27-2004). N Engl J Med 2004;351:912-922.
Robertson D, ed. Primer on the autonomic nervous system. 2nd ed. New York: Elsevier Academic Press, 2004:309.
Schatz I. Farewell to the "Shy-Drager syndrome." Ann Intern Med 1996;125:74-75.
Kaufman H. Consensus statement on the definition of orthostatic hypotension, pure autonomic failure and multiple system atrophy. Clin Auton Res 1996;6:125-126.
To the Editor: The clinicopathological report about a 79-year-old woman with gait, cognition, and autonomic disturbances centered on differential diagnostic features of multiple-system atrophy. Most patients with multiple-system atrophy have orthostatic hypotension. Indeed, the report by Shy and Drager1 that led to the eponym the Shy–Drager syndrome was entitled, "A Neurological Syndrome Associated with Orthostatic Hypotension." The term "multiple-system atrophy" replaced the eponym in the mid-1990s.2 The case presentation should have noted whether the patient had normal or abnormal orthostatic blood pressure instead of mentioning only that "her vital signs were normal." Moreover, because of poor baroreflex function associated with multiple-system atrophy,3 the patient may have also had a constant pulse rate despite having orthostatic hypotension — another abnormal and pertinent finding. In regard to the use of laboratory testing to distinguish multiple-system atrophy from Parkinson's disease, more than 20 studies worldwide have shown that Parkinson's disease entails decreased or absent cardiac sympathetic innervation, whereas multiple-system atrophy does not; this finding may prove important not only for differential diagnosis,4 but also for understanding the pathogenetic mechanisms of the two diseases.
David S. Goldstein, M.D., Ph.D.
National Institute of Neurological Disorders and Stroke
Bethesda, MD 20892-1620
goldsteind@ninds.nih.gov
References
Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension: a clinical-pathological study. Arch Neurol 1960;2:511-527.
Schatz I. Farewell to the "Shy-Drager syndrome." Ann Intern Med 1996;125:74-75.
Goldstein DS, Pechnik S, Holmes C, Eldadah B, Sharabi Y. Association between supine hypertension and orthostatic hypotension in autonomic failure. Hypertension 2003;42:136-142.
Braune S. The role of cardiac metaiodobenzylguanidine uptake in the differential diagnosis of parkinsonian syndromes. Clin Auton Res 2001;11:351-355.
To the Editor: In the discussion of management in the August 26 Case Record, Dr. Hamann does not say how long the patient survived after she met the criteria for enrollment in hospice. If the doctors associated with the patient's hospice predicted that she had less than six months to live at four years, three years, two years, and one year before her actual death, then these differences between prediction and observation are part of the data of Dr. Hamann's case and should be reported. In a similar fashion, the sources of the (incorrect) prognoses should be cited and discussed. A 1999 study1 that used criteria from the National Hospice Organization's "Medical Guidelines for Determining Prognosis in Selected Non-Cancer Diseases"2 found that hospice criteria were not accurate in predicting survival in a group of 2600 patients with advanced chronic obstructive pulmonary disease, congestive heart failure, or liver disease; in a subgroup that was predicted to have less than a 10 percent chance of living for six months, 41 percent survived for more than six months.
Richard A. Martin, M.D.
9448 W. Edgar Earl Loop
Crystal River, FL 34428
References
Fox E, Landrum-McNiff K, Zhong Z, Dawson NV, Wu AW, Lynn J. Evaluation of prognostic criteria for determining hospice eligibility in patients with advanced lung, heart, or liver disease. JAMA 1999;282:1638-1645.
Stuart B, Alexander C, Arenella C, et al. Medical guidelines for determining prognosis in selected non-cancer diseases. 2nd ed. Alexandria, Va.: National Hospice and Palliative Care Organization, 1996.
The authors reply: Dr. Goldstein inquires about orthostasis in our patient, mentions testing of cardiac innervation for diagnostic accuracy, and raises the issue of pathogenesis. During the first three years of our patient's illness, there were no detectable abnormalities in blood pressure or heart rate, but she declined to undergo formal autonomic testing. During the final year of her life, postural dizziness was observed with passive transfers, but orthostasis was not recorded.
Reports of a loss of sympathetic cardiac innervation in Parkinson's disease relied on detection by radioligands, such as 6-[18F]fluorodopamine.1 Progressive dysinnervation was found in sporadic cases and in familial forms of the disease with mutations in the -synuclein gene. These studies suggested that degeneration of peripheral, postganglionic sympathetic neurons in Parkinson's disease was a result of abnormal -synuclein metabolism.1 In contrast, autonomic dysfunction in multiple-system atrophy arises chiefly from degeneration in the central nervous system and of preganglionic cells,2 although -synuclein deposits have been described in peripheral gangliocytes in a few cases. We concur with Dr. Goldstein that the distinction between multiple-system atrophy and Parkinson's disease with dysautonomia has been improved by monoaminergic radiolabeling studies.3
Dr. Schatz identifies an editing error by Dr. Schlossmacher, who misused the word "pure" in characterizing autonomic failure in multiple-system atrophy (the Shy–Drager syndrome). As a disease of the peripheral nervous system, pure autonomic failure lacks involvement of the central nervous system and, thus, signs of parkinsonism or cerebellar dysfunction. Adding to the complexities in nomenclature and pathophysiology, pure autonomic failure shares with Parkinson's disease the predilection for postganglionic neurons and the characteristic, intraneuronal accumulation of -synuclein.4
Dr. Martin asks whether our patient exemplified the known inaccuracy of predicting death within six months of hospice enrollment. During the last six months of her life, she resided in a nursing home that provided full palliative care and did not need a hospice referral. In general, we favor a hospice approach for patients with advanced neurodegenerative diseases.5
Michael G. Schlossmacher, M.D.
Claus Hamann, M.D.
Harvard Medical School
Boston, MA 02115
mschlossmacher@rics.bwh.harvard.edu
References
Singleton A, Gwinn-Hardy K, Sharabi Y, et al. Association between cardiac denervation and parkinsonism caused by alpha-synuclein gene triplication. Brain 2004;127:768-772.
Benarroch EE, Schmeichel AM, Low PA, Parisi JE. Involvement of medullary serotonergic groups in multiple system atrophy. Ann Neurol 2004;55:418-422.
Riley DE, Chelimsky TC. Autonomic nervous system testing may not distinguish multiple system atrophy from Parkinson's disease. J Neurol Neurosurg Psychiatry 2003;74:56-60.
Arai K, Kato N, Kashiwado K, Hattori T. Pure autonomic failure in association with human alpha-synucleinopathy. Neurosci Lett 2000;296:171-173.
Volicer L, Hurley A. Hospice care for patients with advanced progressive dementia. New York: Springer, 1998.