American Academy of Neurology qualifications and guidelines for the physician expert witness.
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Biomedical subjects
Publications and source records attributed to M P McQuillen.
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The growth of bioethics as a practical, meaningful player in the arena of health care has paralleled that of clinical neurology not only in time but also in interaction between the two disciplines. Almost every advance in neurology has spawned an ethical dilemma, the unraveling of which has brought new insights to both fields of endeavor. The myriad ways in which this parallel growth has touched one clinical neurologist, the persons with whom he has been privileged to work, and those for whom they have cared is offered in reflection on the meaning of ethics, the essence of concepts such as "brain death," the pain of truth telling, the complexity of informed consent, the societal dimension of the "vegetative state," and finally, even the business of medicine. Should readers not find any pearls of wisdom in this offering, the author can at least hope it will prevent them from falling into the same pits.
Conflicts of interest are inherent in the practice of medicine, particularly in the conduct of clinical research. Such conflicts can often be identified and even resolved by the application of ethical principles as an integral part of such research. The opportunity to participate in a series of controlled clinical trials of therapeutic plasma exchange (TPE) in diverse neurologic disease provided an insight into some of the ethical dilemmas posed by such conflicts of interest. Chief among these was the recognition that informed consent is a precious though fragile and multidimensional concept. In the last analysis, ethics is the "business of being human"; respect for its guidance helps to ensure the success of clinical research.
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The transformation of American medicine now taking place is fundamentally driven by money. As the pendulum swings from the excesses of fee-for-service medicine (under which system the physician was paid more for doing more), to the equally egregious excesses of managed care (according to which the physician is paid more for doing less), it is the patient--especially the vulnerable patient with a debilitating neurological disease--who stands to lose the most. A survey of the historical roots of this transformation highlights the ethical dilemmas under the course of the pendulum. The ethical principles that should guide both the profession and the business of medicine are explored in search of a common ground on which both physicians and managers can work in concert for the benefit of the patients as well as the society whom both serve. The perils that beset that search must be recognized and avoided if the commons are to be preserved. This is especially true for neurology, where care must be patient, not profit, oriented; must have quality, not cost, as its primary aim; and must not be rationed until there is a floor of universal coverage, with participation by all in allocation decisions.
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A woman with previously treated disseminated histoplasmosis was admitted with progressive paraparesis. Magnetic resonance imaging showed multifocal cerebritis and spinal histoplasmoma. She recovered following a second treatment with amphotericin B. This is the fourth reported patient with intramedullary spinal histoplasmoma, and the first demonstrating successful treatment of the lesion with medical therapy alone.
Three hundred twelve patients were entered into a long-term study of effects of hyperbaric oxygen on multiple sclerosis. The protocol called for an initial 20 treatments in either the monoplace or multiplace chamber on a daily basis followed by monthly booster treatments for 2 years. One hundred seventy neurologists and 22 institutions provided data for this study. There was no control group, but the study was based on Schumacher's postulation that a scientifically valid study to test the efficacy of a new therapy was possible by choosing patients who were definitively diagnosed with multiple sclerosis and following them up for 2 years after the imposed treatment. If the overwhelming majority of the subjects failed to get worse over the 2-year observation period, the efficacy of the treatment would be manifest. The expanded Kurtzke Disability Status Scale (EDSS) was used to assess the severity of the disease state. The dropout rate was high with only 76% (237 of 312 patients) finishing the initial 20 treatments. Twenty-two percent (69 of 312) finished 1 year of booster therapy, and 9% (28 of 312) completed 2 years of monthly boosters. The mean deterioration on the Kurtzke EDSS score was 0.93 or almost a full step from the beginning of treatment until the last evaluation. There was no difference in outcome between those who had the shortest and longest periods of time between onset of symptoms and hyperbaric oxygen treatment. Treatment pressure made no difference in outcome. Changes in the Kurtzke EDSS score bore no relationship to the use of booster treatment. Patients who were reasonably well off at the onset of treatment with initial Kurtzke EDSS scores of 1 or 2 (n = 21) deteriorated by an average of 1.7 Kurtzke points. Those patients whose initial Kurtzke EDSS scores were greater than 2 (n = 164) deteriorated on an average of 0.82 points. Of interest was that 19.5% (39 of 200) of the patients reported a temporary improvement in bladder function, but improvement was maintained in only 11 patients (5.5%) at 2-year follow-up. Fifteen patients (7.5%) indicated long-term worsening. There was no significant change in the working status of the patients following hyperbaric oxygen treatment. Although this study treated the patients in accordance with protocols reported to produce a benefit in multiple sclerosis, we were unable to substantiate any useful long-term effect of hyperbaric oxygen therapy.
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Plasma exchange (PE) was shown in a previous double-blind randomized controlled study to confer significant additional benefit at 1 year upon patients with chronic progressive multiple sclerosis (CPMS) treated with immunosuppressive drug therapy (ISDT). Efficacy over an extended term, indications for retreatment, and long-term toxicity are dealt with in this analysis of a larger number of patients. During the past 7 years, 200 patients with CPMS have been treated with PE and low-dose ISDT at this center. Improvement on the Kurtzke Disability Status Scale by one or more steps post-therapy and at 3-year follow-up is significant by comparison with pre-PE disability status. Clinical improvement was maintained in the majority of patients, reaching as far as a 6-year follow-up. Major life-threatening complications attributable to this combined therapy were not observed.
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We enrolled 116 patients in a multicenter, randomized, double-blind controlled trial of an 8-week course of 11 plasma exchange (PE) treatments in exacerbations of MS. The control group received sham PE, and both groups received identical treatment with IM ACTH and oral cyclophosphamide. Serum IgG decreased in the PE and sham treatment groups by 76% versus 22% by treatment 5, and by 64% versus 14% by treatment 11. PE also produced significant reductions in IgA, IgM, C3, and fibrinogen. PE patients had moderately enhanced improvement at 2 weeks relative to the sham group. PE patients with relapsing/remitting disease had significantly enhanced improvement at 4 weeks and there was also an increased improvement at 12 months, although this latter effect disappeared when we analyzed relapsing/remitting patients as a separate subgroup. Life table analysis showed the median time to recover preattack disability status was shorter in PE- than in sham-treated relapsing/remitting patients (4 vs. 13 weeks), a result confirmed by raw disability status scores in which there was recovery to their average preattack disability score by 3 months. PE given with ACTH plus cyclophosphamide enhances recovery from an exacerbation of disease in relapsing/remitting patients, although we observed no clear long-term benefits.
BMT has become an important therapy for many hematologic disorders. Following BMT, the recipient may develop GVHD when it appears that immunocompetent donor lymphocytes react to host antigens. Acute and chronic GVHD represent two distinct syndromes. Acute GVHD has not been associated with primary neurologic involvement. Polymyositis has been reported in 12 patients with chronic GVHD, with the most common underlying illness being aplastic anemia. The clinical, serologic, and muscle biopsy features of the myositis in GVHD have been similar to those observed in idiopathic polymyositis. Weakness was moderate to severe and responded to prednisone, sometimes with the addition of azathioprine. Prognosis depended upon the underlying disease and not on the severity of the myositis. MG occurs rarely in chronic GVHD. Most patients with MG and GVHD have had aplastic anemia; those with aplastic anemia are more likely to have anti-AchR prior to BMT. The clinical manifestations of GVHD MG have not differed from classic autoimmune MG; each patient had elevated antiacetylcholine receptor antibodies titers. All patients have responded well to cholinesterase inhibitors but have received other immunosuppressants. These observations suggest that aplastic anemia is an important host factor in the development of the autoimmune disorders seen with chronic GVHD, certainly of myositis and MG. Herpes zoster peripheral nerve infections have occurred in patients with chronic GVHD. One patient had mononeuritis multiplex. In both acute and chronic GVHD, CNS impairment is usually caused by metabolic encephalopathy or infection. Primary CNS involvement has not been recognized.