posure to sciatic nerve antigen (four of seven cases), but ... tients with Hodgkin's disease or lymphoma in ... demyelination of peripheral nerve in tissue culture.
EDITORIALS
respiratory centers. Damage the reticular formation, therefore, and one necessarily damages at least some of these other structures too, so that pupillary, oculovestibular and respiratory abnormalities are present from the beginning and point directly to a lesion in the stem. Often, but not always, the brain stem lesions lie more to one side than the other, so that one finds asymmetrical signs of neurological abnormality in the stem itself combined with asymmetrical long tract motor abnormalities below that point. Metabolic encephalopathy is by far the commonest cause of unconsciousness in general hospitals. Clinically, most patients with metabolic coma appear to have more depression of forebrain than of brain stem. However, the striking and diagnostic finding with most metabolic agents is that they selectively depress certain susceptible functions at several different levels of the brain but at the same time spare other functions which equally depend on structures at those self-same levels. Obviously, no mechanical lesion could at one and the same time possess this combination of launching both a diffuse and a selective attack. There are other helpful clues: most metabolic encephalopathies cause delirium in advance of stupor or coma and many of them are accompanied by various forms of tremor or myoclonus in their pre-coma stage. Almost all metabolic comas spare the pupillary light reflex (the examining physician must use a bright light and beware of overlooking a brisk response) and many of them spare or even enhance oculovestibular responses as well. Respiratory changes are common with metabolic coma, often because the disease itself produces acid-base changes. Although the metabolic encephalopathies occasionally may produce asymmetrical signs, they usually do not and they never impair central sensory pathways except as a part of the overall depression of consciousness. Psychogenic unresponsiveness can externally copy organic coma, but the clinical fine points give it away. The diagnostic key is that patients with psychogenic responsiveness are behaviorly abnormal but physiologically normal. Not surprisingly, therefore, shouting, pinching and various other traumatic assaults have an unpredictable effect or none at all. This stands in contrast to the normal results of physical examination-normal breathing, intact pupils, preserved quick-phase nystagmus on caloric tests,4 normal muscle resistance and stretch reflexes, and the absence of abnormal reflexes. Fisher5 perceptively pointed out
that such patients often actively close the eyelids when they are pressed open by the examining physician, whereas the lids shut more gently in true coma. If any doubt persists, it is reassuring to have a normal electroencephalogram and an examination of the cerebrospinal fluid. More invasive studies are unnecessary. Does this clinical approach always work? Of course not-nothing in biology always works; but when it has not, we usually have found that the problem lay in our own not asking enough, not looking enough or not examining enough, rather than in our not plunging forward with more screening laboratory tests. FRED PLUM, MD Anne Parrish Titzell Professor of Neurology New York Hospital-Cornell Medical Center
REFERENCES 1. Magoun HW: The Waking Brain, 2nd Ed. Springfield, 111., Charles C Thomas, 1963 2. Mangold R, et al: Effects of sleep and lack of sleep on cerebral circulation and metabolism of normal young men. I Clin Invest 34:1092-1100, 1955 3. Plum F, Posner JB: The Diagnosis of Stupor and Coma, 2nd Ed. Philadelphia, Davis, 1972 4. Nelson JR: The minimal ice water caloric test. Neurology 19:577-585, 1969 5. Fisher CM: The neurological examination of the comatose patient. Acta Neurol Scand 45: Suppl 36:1-56, 1969
Idiopathic Polyneuritis WITH THE DISAPPEARANCE of acute poliomyelitis in the United States since the institution of massive vaccination campaigns 15 years ago, idiopathic polyneuritis (Landry-Guillain-Barre syndrome) has become the most frequent cause of major paralytic disease. Idiopathic polyneuritis is doubly important to physicians because respiratory assistance and close medical attention are necessary for a time in a considerable proportion of patients, but full recovery without residual weakness may be anticipated in over 80 percent if the acute phase of the illness can be successfully bridged. In this issue of THE WESTERN JOURNAL OF MEDICINE, Rosenberg and Mendoza present a case in point in a Specialty Conference. The patient discussed was an adolescent boy with typical idiopathic polyneuritis who would surely havet died without expert ventilatory assistance, but who at last report seemed well on the way to recovery. Although the ability to manage patients with idiopathic polyneuritis has improved considerably in recent years, our understanding of the THE WESTERN JOURNAL OF MEDICINE
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EDITORIALS
basic mechanism of the disorder is far from complete. Interest in the pathogenesis of idiopathic polyneuritis has grown for half a century, with a veritable flood of studies appearing in the past five years, but the crucial questions have defied resolution. What are the nosologic limits of the entity? Is it one or several diseases? What is the common element in the apparent variety of precipitating events? What is the role of immunologic defense mechanisms? What other host factors are involved? Several lines of evidence suggest that idiopathic polyneuritis, like experimental allergic neuritis, is mediated by sensitized lymphocytes, that is, is a disorder of delayed hypersensitivity. First, the pathological hallmark is perivenular lymphocytic and mononuclear cell infiltration.' Second, buffy coat cells from patients with idiopathic polyneuritis will regularly, but not always, demyelinate cultures of myelinating rat trigeminal ganglion.2 Third, lymphocytes from patients with idiopathic polyneuritis will elaborate the lymphokinin, macrophage migration inhibitory factor, following exposure to sciatic nerve antigen (four of seven cases), but lymphocytes from patients with other neuropathies will not.3 Similar kinds of evidence have been reported by Knowles and coworkers4 and by Cook et al.5 Fourth, recent electron microscopic studies have delineated how macrophages in the presence of lymphocytes destroy myelin sheath in a distinctive pattern which is identical both in idiopathic polyneuritis6 7 and experimental allergic neuritis.8 Other lines of evidence either cast doubt on the delayed hypersensitivity concept or point to alternative, particularly humoral, mechanisms. Drachman et a19 reported typical idiopathic polyneuritis occurring in a severely immunosuppressed patient who had undergone renal transplantation. Other well-documented examples have occurred in patients with Hodgkin's disease or lymphoma in whom serious immuno-deficiency would be expected. A host of other studies implicate circulating factors, presumably humoral antibodies, in idiopathic polyneuritis.'0-'5 Finally, preceding viral infection seems to play an important role in many cases. More than 50 percent of patients give a history of viral-like illness in the preceding one to four weeks. Usually such preceding illnesses remain undiagnosed, but many known viral infections have been followed by idiopathic polyneuritis including acute exan154
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thems,'6 small pox vaccination,'7 Epstein-Barr virus infection,'8 cytomegalovirus,"9 and serum hepatitis.20 Other non-viral preceding events have included surgical operation one to four weeks before,2' antirabies vaccination containing dessicated rabbit spinal cord and roots,22 fever therapy,23 and mycoplasma infection.24 Tantalizing as these fragments of evidence are, they do not allow synthesis of a fully satisfying story. Nevertheless they sluggest that some event, common to a wide range of trivial assaults upon the human body, triggers a misdirected immunological response that culminates in widespread peripheral myelin destruction. ARTHUR K. ASBURY, MD Professor and Vice-Chairman Department of Neurology University of California, San Francisco; Chief, Neurology Service San Francisco Veterans Administration Hospital REFERENCES 1. Asbury AK, Arnason BG, Adams RD: The inflammatory lesion in idiopathic polyneuritis. Medicine 48:173-215, 1969 2. Arnason BGW, Winkler GF, Hadler NM: Cell-mediated demyelination of peripheral nerve in tissue culture. Lab Invest 21:1-10, 1969 3. Rocklin RE, Sheremata WA, Feldman RG, et al: The Guillain-Barre syndrome and multiple sclerosis: in vitro cellular responses to nervous-tissue antigens. N Engl J Med 284:803-808, 1971 4. Knowles M, Saunders M, Currie S, et al: Lymphocyte transformation in the Guillain-Barr6 syndrome. Lancet 2:1168-1170, 1969 5. Cook SD, Dowling PC, Whitaker JN: The Guillain-Barre syndrome: Relationship of circulating immunocytes to disease activity. Arch Neurol 22:470474, 1970 6. Prineas JW: Acute idiopathic polyneuritis: An electron microscope study. Lab Invest 26:133-147, 1972 7. Wisniewski H, Terry RD, Whitaker JN, et al: Landry-Guillain-Barr6 syndrome: A primary demyelinating disease. Arch Neurol 21:269-276, 1969 8. Lampert PW: Mechanism of demyelination in experimental allergic neuritis: Electron microscopic studies. Lab Invest 20:127138, 1969 9. Drachman DA, Paterson PY, Berlin BS, et al: Immunosuppression and the Guillain-Barre syndrome. Arch Neurol 23:385-393, 1970 10. Yonezawa T, Robbins N, Ishihara Y, et al: In vitro demyelination produced by sera from Landry-Guillain-Barre syndrome. Proc VIth Internat Congress Neuropathology 688-689, 1970 11. Tse KS, Arbesman CE, Tomasi TB, et al: Demonstration of antimyelin antibodies by immunofluorescence in Guillain-Barr6 syndrome. Clin Exp Immunol 8:881-887, 1971 12. Cook SD, Dowling PC, Murray MR, et al: Circulating demyelinating factors in acute idiopathic polyneuropathy. Arch Neurol 24:136-144, 1971 13. Dubois-Dalcq M, Buyse M. Buyse G, et al: The action of Guillain-Barre syndrome serum on myelin: A tissue culture and electron microscopic analysis. J Neurol Sci 13:67-83, 1971 14. Luijten JAFM, Baart De La Faille-Kuyper EH: The occurrence of 1gM and complement factors along myelin sheaths of peripheral nerves: An immunohistochemical study of the GuillainBarr6 syndrome. J Neurol Sci 15:219-224, 1972 15. Link H: Immunoglobulin abnormalities in the GuillainBarr6 syndrome. J Neurol Sci 18:11-23, 1973 16. Miller HG, Stanton JB, Gibbons JL: Para-infectious encephalomyelitis and related syndromes. Quart J Med 25:427-504, 1956 17. Spillane JD, Wells CEC: The neurology of Jennerian vaccination. Brain 87:1-44, 1964 18. Grose C, Feorino PM: Epstein-Barr virus and GuillainBarre syndrome. Lancet 2:1285-1287, 1972 19. Leonard JC, Tobin JO'H: Polyneuritis associated with cytomegalovirus infections. Quart J Med 40:435-442, 1971 20. Asbury AK: Hepatic neuropathy, Chapter In Peripheral
EDITORIALS Neuropathy, P. J. Dyck, P. K. Thomas, and E. H. Lambert, Editors In press, 1973 21. Arnason BG, Asbury AK: Idiopathic polyneuritis after surgery. Arch Neurol 18:500-507, 1968 22. Appelbaum E, Greenberg M, Nelson J: Neurological complications following antirabies vaccination. JAMA 151:188-191, 1953 23. Garvey PH, Jones N, Warren SL: Polyradiculoneuritis (Guillain-Barr6 syndrome) following the use of sulfanilamide and fever therapy. JAMA 115:1955-1959, 1940 24. Steele JC, Gladstone RM, Thanasophon S, et al: WMcoplasma pneumoniae as a determinant of the Guillain-Barr6 syndrome. Lancet 2:710-713, 1969
PSRO-Update 1974 IT IS NOW a little more than a year since the Professional Standards Review Organization (PSRO) legislation went into effect. So far its implementation is on schedule. As required by PL 92-603, the PSRO areas were designated on 1 January 1974. The legislation gives practicing physicians priority in establishing the PSRO'S for each of these areas at least until 1 January 1976. At that time the Secretary of the Department of Health, Education, and Welfare may designate other "qualified" public or non-profit organizations as the PSRO for a given area, as he deems it necessary. The main interest of the Congress in adopting the PSRO legislation seems clear enough. It is to reduce the cost of the Medicare and Medicaid programs by imposing utilization controls on the services provided to the beneficiaries. The Senate Report on why the PSRO legislation was enacted states: "There is no question that the Government has a responsibility to establish mechanisms capable of assuring effective utilization review. Its responsibility is to millions of persons dependent upon Medicare or Medicaid, to the taxpayers who bear the burden of billions of dollars in annual program costs, and to the health care system." The assumption that is made is also clear. It is assumed that simply by eliminating excessive utilization the cost of these programs will somehow be contained, and it is assumed that this can be done without impairment of quality. However, there are many physicians who seriously question the validity of these assumptions, and there is considerable reason to believe that quality and cost are closely and inextricably linked in medical care.
The PSRO legislation also addresses itself to the
quality of the medical care for which payments are to be made under Medicare, Medicaid and Maternal and Child Health programs. This aspect is emphasized in a brochure recently given wide distribution to physicians by the Assistant Secretary for Health. The brochure states: "The primary emphasis of the PSRO program is on assuring the quality of medical care. Providing quality care may increase health services for some patients in certain areas and could increase costs in those circumstances. "A PSRO will be concerned also with whether medical care is necessary and delivered in the proper setting. If overuse or uneconomical use of services are identified and eliminated, cost savings will result. "A PSRO will not concern itself in any way with the fees for services charged by physicians or institutions." Cost containment and quality assurance are both desirable and essential. But if it should happen to turn out that assuring quality and reducing costs cannot be accomplished at the same time by the means proposed by the PSRO legislation, many physicians believe that something of a crunch may be anticipated. In these circumstances it is quite possible that practicing physicians and the medical profession may be held responsible and to blame for the failure. This is hardly a comforting prospect for working doctors who are already the hapless victims of discriminating fiscal sanctions imposed by a more or less arbitrary government, and from which the medical profession is still finding itself with little or no recourse. To accomplish its goals the approach of the PSRO legislation is to develop norms and standards for medical care. Initially these are to be established locally to meet local customs and needs as determined by the locally designated PSRO, but it is clearly expected that regional and perhaps even national standards will eventually ensue. The assumption seems to be that similar cases can be given similar care and that this will somehow be more economical, and that dissimilar cases requiring dissimilar case care will somehow be handled as occasional exceptions by the local PSRO. These assumptions of course strike at the heart of medical practice and medical care. A basic question is whether the good quality of care to which most Americans are accustomed and to which all Americans aspire can ever really be standardized, or if quality is to be preserved, will the exceptions THE WESTERN JOURNAL OF MEDICINE
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