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Chiropractic management of a patient with myasthenia gravis and vertebral subluxations
Journal of Manipulative and Physiological Therapeutics Volume 22 • Number 5 • June 1999 0161-4754/99/$8.00 + 0 76/1/98562 © 1999 JMPT
CASE REPORTS Chiropractic Management of a Patient with Myasthenia Gravis and Vertebral Subluxations Joel Alcantara, DC,a David M. Steiner, DC,b Gregory Plaugher, DC,c and Joey Alcantarad
ABSTRACT Objective: The chiropractic management of a patient with myasthenia gravis and vertebral subluxation is described. We discuss the pathophysiology, clinical features, and treatment of patients with these diseases. Clinical Features: The 63-year-old male patient suffered from complaints associated with the disease myasthenia gravis along with signs of vertebral subluxation. The patient had an initial complaint of dysphagia. In addition, the patient experienced swelling of the tongue, nausea, digestive problems, weakness in the eye muscles, difficulty breathing, myopia, diplopia, and headaches. Balance and coordination problems resulted in walking difficulties.
INTRODUCTION The English physician Thomas Willis first described the clinical syndrome of myasthenia gravis in 1672.1 In 1895 Jolly named the disease, “myasthenia gravis pseudoparalytica.”2 In the Americas in the 1600s, the Indian chief Opechankanough may have been the first American identified with the disease.3 According to a 1994 estimate, approximately 36,415 patients have myasthenia gravis in the United States, and the number of people in whom myasthenia gravis will develop is estimated at 1014 per year.4,5 Myasthenia gravis is an autoimmune disorder with patient complaints of voluntary muscle weakness. The distribution of weakness may involve the ocular, facial, oropharyngeal,
a Assistant Professor, Palmer College of Chiropractic West, San Jose, California, and Research Associate, Gonstead Clinical Studies Society, Mt. Horeb, Wisconsin. b Private Practice of Chiropractic, Miramar, Florida c Associate Professor, Life Chiropractic College West, San Lorenzo, California, and Director of Research, Gonstead Clinical Studies Society, Mt. Horeb, Wisconsin. d Chiropractic Intern, Palmer College of Chiropractic West and Professional Member, Association of Professional Engineers, Geologists and Geophysicists of Alberta (APEGGA), Canada. Submit reprint requests to: Joel Alcantara, BSc, DC, Palmer Center for Chiropractic Research, Palmer College of Chiropractic-West, 90 E Tasman Dr, San Jose, CA 95134; [email protected]. Paper submitted April 27, 1998; in revised form May 18, 1998. Funded by Palmer College of Chiropractic West, San Jose, California and the Gonstead Clinical Studies Society, Mount Horeb, Wisconsin.
Intervention and Outcome: Contact specific, highvelocity, low-amplitude adjustments were applied to sites of patient subluxation. Myasthenia gravis is no longer debilitating to the patient; he is medication free and has resumed a “normal life.” Conclusion: The clinical aspects of the disease, including the possible role of chiropractic intervention in the treatment of patients suffering from myasthenia gravis, are also discussed. This case study encourages further investigation into the holistic approach to patient management by chiropractors vis-à-vis specific adjustments of vertebral subluxation. (J Manipulative Physiol Ther 1999;22:333-40) Key Indexing Terms: Myasthenia Gravis; Chiropractic; Dysphagia
and limb muscles. Not surprisingly, the cranial nerves are almost invariably involved, in particular cranial nerves III, IV, VI, and VII. Most patients therefore have ptosis, diplopia, dysarthria, and dysphagia. The weakness has characteristic features of fluctuations and variability leading to perceptible exacerbations and remissions.6,7 Sensory deficits of any consequence are rare and may be attributable to concomitant disorders such as diabetic neuropathy or rheumatoid arthritis. Diagnosis is confirmed by the unequivocal and reproducible improvement after intravenous administration of the rapidly acting anticholinesterase drug, edrophonium chloride, otherwise known as Tensilon.8 We report on the chiropractic management of a patient with myasthenia gravis and discuss the relevant clinical features of the disease, including the possible role of chiropractic intervention(s).
CASE REPORT On June 23, 1996, a 63-year-old man sought care, complaining of signs and symptoms related to myasthenia gravis. He had suffered from this disease for approximately 30 years. His reason for this visit was an inability to swallow. The patient related that he would often have to massage his throat for the food to move down his esophagus. He described feeling as if he was going to choke to death. In addition, he experienced swelling of the tongue, weakness in the eye muscles, difficulty breathing, diplopia, myopia, digestive problems, nausea, and headaches. He also reported walking difficulties resulting from problems with balance and coordination. In 1975, 6 years after being diagnosed with myasthenia gravis, the patient underwent a thymecto-
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Fig 1. Radiographic study demonstrates the lateral view of the cervical spine.
my. Before the surgery, the patient was wheelchair bound because of muscle weakness and motor control problems. After the thymectomy he became ambulatory once again, and his breathing improved. Medical management before chiropractic consultation included plans of placing him in an iron lung because of breathing difficulties. At the time of chiropractic consultation, the patient was taking the prescription drug pyridostigmine (Mestinon) 3 to 4 times per day. In spite of the medication, the patient would still experience the above-mentioned signs and symptoms. Physical examination findings noted the following. His shoulder height was higher on the left. His left hip (gluteus maximus) appeared to be narrower than his right. Temposcope skin temperature differentials were noted at the C7 and T4 spinal levels. Motion palpation findings at these levels showed restrictions. Edema, muscular hypertonicity, and tenderness to palpation were also notable at the C7 and T4 area. Full-spine radiographs were obtained. The lateral radiographs reveal a loss of the cervical lordosis (Fig 1). Spondylosis was noted predominately at the C5/C6 vertebral levels, with the C5/C6 and C6/C7 disc spaces diminished. In addition, osteophyte formations were notable mainly at the anterior end plates of the C5 and C6 spinal levels. The C7 vertebral body was noted to be in an extension malposition, with the disc space wider at the anterior and
narrower at the posterior. The patient’s lumbopelvic lateral radiograph demonstrated hypolordosis (Fig 2). The anteroposterior view revealed a pelvic tilt to the left in part because of a 7-mm left femoral head-height deficiency. The obturator foramen on the right appeared to be narrower, and on the left it appeared wider. This is indicative of rotation in the pelvis (ie, external rotation of the left ilium). There appeared to be a tilting of the spine starting at the patient’s mid to upper back, probably because of a lateral flexion misalignment at the T4 vertebral level. There appeared to be a welldelineated calcified lesion posterior to the C6 and C7 spinous processes indicating a possible old spinal injury. The primary subluxation adjusted were predominately located at the C7 and T4 spinal levels. On occasion the patient presented to the treating chiropractor complaining of hip pain. An adjustment to his pelvis on the basis of subluxation findings would be applied, resulting in a favorable outcome. After a total of 33 visits, the patient was instructed to come in once or twice a month or on an “as-needed” basis. The patient continued to visit the treating chiropractor on a regular basis. During the course of a year, the patient had flare-ups and needed to be seen more frequently. The flare-ups consisted primarily of complaints of weakness in his left eye. His left eyelid became weak and drooped, interfering with proper vision, as well as producing diplopia. On January 29, 1997, the patient presented for treatment with his left eye closed. He stated that it had been that way for the past week and seemed to be getting worse. After five adjustments in 5 visits, the patient reported that his left eyelid had started to open up since the five treatments began. By April 11, 1997 (or after 12 adjustments), he indicated further improvement in his left eye complaint. By May 16, 1997 (or 13 visits), he related that his left eye was “perfect” and that it remained open continuously. The patient denied weakness in the left eye muscles; there was an absence of droopiness in the eyelid, and the diplopia was no longer present. The patient indicated that he started to notice improvement within the first 2 weeks of care, and as treatment continued, he felt better and better, eventually being weaned off his medication. During the course of his treatment by the chiropractor, the patient was also monitored by his medical doctor. The patient continues to be medication free. Even with the exacerbation of his left eye, he was able to overcome it exclusively by receiving adjustments to the cervical spine. His last visit to the treating chiropractor was on June 24, 1997. At that time, the patient reported that he was not experiencing any signs or symptoms of myasthenia gravis. When he first presented to the treating chiropractor, the patient was semiretired and working with no regularity. Presently, he is working full-time as a businessman.
DISCUSSION Pathophysiology Myasthenia gravis is an autoimmune disorder that affects the skeletal muscles. The pathophysiology of the disease involves the presynaptic nerve terminal and structures locat-
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Fig 3. Radiographic study demonstrating the anteroposterior view of the lumbopelvis.
Fig 2. Radiographic study demonstrates the lateral view of the lumbopelvis.
ed in the postsynaptic skeletal muscle membrane. In a simplistic approach, we provide the following description of the disease. For a more extensive discussion on the topic, we refer the reader elsewhere.9-11 Calcium entry into the nerve terminal at a neuromuscular junction triggers the release of acetylcholine (ACh) from storage vesicles within the nerve terminal.12 Each synaptic vesicle releases about 10,000 ACh molecules into the synaptic cleft,13 where it diffuses rapidly throughout. At the postsynaptic membrane, acetylcholine receptors (AChR) line the primary synaptic clefts. The membrane itself contains depressions resulting from membrane in-folding to increase membrane surface area. The AChR is a transmembrane glycoprotein structure composed of 5 subunits that is cation-selective and ligand gated.14 In a possible ligand-receptor interaction put forth, the binding of ACh may somehow cause the AChR subunits to move and portions of the transmembrane protein may form a gate that opens.14 Opening of these gates is a requisite for ion permeability, membrane depolarization, and a resultant action potential for muscle contraction. In myasthenia gravis antibodies generated by the immune system attack the AChR. The resultant antibody-receptor structure may result in receptor blockade. The main immunogenic regions are
located close to but distinct from the subunit of the AChR.14,15 Another possibility from an antibody-receptor interaction perspective is that the AChR structure may be altered, resulting in poor affinity of the ACh for the receptor. The resultant size or duration of a single channel current because of the ion permeability or the duration of opening burst of the receptor gates may thus be affected.14,16 Overall, regardless of the specific effect of AChR binding by antibodies, the result is an inadequate response to ACh release and therefore muscle response.
Diagnosis Myasthenia gravis is a common disease of the neuromuscular junction and is considered fairly stereotypical. For example, most patients have ptosis, ophthalmoplegia, dysarthria, and dysphagia. Myasthenia gravis is known as the “great imitator” because it may mimic cranial nerve palsies and brainstem diseases, myopathies, and anterior horn cell disease.17 It is beyond the scope of this writing to delve into great detail with respect to diagnosis, and the reader is referred elsewhere.18 The demonstration of weakness with continued use and improvement in strength with a short rest is diagnostic. The patient may be referred to a medical doctor for the Tensilon test, which is readily available. However, some caveats are worth mentioning, because this test has associated risks. The drug may be dangerous and life threatening, particularly to the elderly, those with
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heart disease, and individuals with obstructive lung disease. Also the test may be difficult to interpret and difficult to tell from placebo, especially when the complaint of weakness is mild.17 Immunologic testing for the AChR is very reliable. However, false-positive results may occur in some patients, such as those with systemic lupus erythematosus.19 Finally, electrophysiological testing may also be performed, and the reader is referred elsewhere for a more complete discussion20 on the topic.
Medical Treatment The goal of any treatment regimen, medical or otherwise, is to produce normal function. The ideal therapy should have rapid onset with minimal side effects, be easy to administer, and have low cost. The following is a cursory overview of some of the medical approaches to the disease, based on the work by Massey.21 Cholinesterase inhibitors are usually used as the initial therapy. They provide symptomatic improvement for a time by hindering the hydrolysis of acetylcholine at the neuromuscular junction. However, this approach alone is rarely sufficient. Pyridostigmine bromide (Mestinone) and neostigmine bromide (Prostigmine) are the most commonly used agents. Common side effects are gastrointestinal hyperactivity and increased upper and respiratory secretions, as well as bradycardia. Thymectomy is another approach to treatment, although no prospective blinded study has ever been performed nor is the association between the thymus and the pathogenesis of myasthenia gravis fully understood. There are reports that more than 50% of patients undergoing thymectomy experience sustained improvement. The use of immunosuppressant drugs is another treatment choice. However, because of the increased risk of infection as a result of the immunosuppression, as well as the potential side effects of the individual drugs, this route of care must be used with caution. The treatment is dependent on the rate of progression and the severity of weakness in patients’ symptoms and the potential side effects of the medication. Immunosuppressant agents used are corticosteroids, azathioprine, cyclosporine, and cyclophosphamide. Other forms of therapy include plasmapheresis, intravenous immunoglobulin, total body radiation, splenectomy, thoracic duct lymph drainage, and anti-thymocyte globulin.
Chiropractic Care This is the second citation in the scientific literature describing the chiropractic management of a patient with myasthenia gravis. Araghi22 reported in a conference proceedings the chiropractic care of a 2-year-old female patient in whom myasthenia gravis developed after a motor vehicle collision. She had the following symptoms after injury: otitis media, ptosis of the right eye (developed 8 days after trauma), lethargy, lower extremity weakness, bilateral toe-in foot flare, and a moderate left head tilt. The patient had a positive Tensilon test result and electromyogram. The patient was adjusted at S2, atlas, and occiput, with the Gonstead technique. Her symptoms were nearly completely
resolved after 5 months of care. The patient presented in this case report was also managed with the Gonstead technique. The technique is an established method of patient management and is highly used within the practice of chiropractic.23 The management approach with respect to examination findings (ie, inspection, palpation, range of motion, spinography and x-ray marking, and Nervoscope instrumentation) and treatment approach (ie, adjustments with respect to patient position, doctor’s stance, patient and doctor’s contact point, line of drive, line of correction, and torque) are well described in the Gonstead reference text by Plaugher and Lopes.24 The patient was treated during a total of 80 visits over a period of approximately 2 years. The main subluxation findings were at C7 PLS, T4 PRI-T, and L5 PL. To delineate the possible role of chiropractic intervention in the treatment of patients suffering from a myriad of conditions, we will examine the effects of treatment from three possible perspectives with respect to patient improvement. One reason why a patient’s condition may improve is due to the natural history of the disease or regression to the mean. That is, regardless of the treatment the patient may receive, the patient’s problems resolve. Regression to the mean refers to the phenomenon in which the patient’s symptoms are to the extreme on first examination and then return to their more natural or typical state, which are not so severe. According to Massey,21 because of 22% of untreated patients achieving remission and another 18% experiencing marked improvement, it is difficult to sort out the effects of any therapeutic improvement on myasthenia gravis from the natural history of the disease. The role of the natural history of this disease is confounded by the patient’s thymectomy some 6 years after being diagnosed with the disease if one is of the opinion that 6 years is not ample time to decide that the disease will not improve. In addition, approximately 30% of patients with myasthenia gravis will experience weakness in the respiratory muscles, and approximately 15% to 20% will experience myasthenia crisis. Myasthenia crisis is defined as respiratory failure requiring mechanical ventilation.25 A study by Durelli et al26 examined the occurrence of remissions in 400 patients who had myasthenia gravis with thymectomy. These patients had an overall stable remission of 27%. Incidentally, Durelli et al26 caution that, in the absence of a concurrent control group of nonthymectomized patients, no definitive conclusions about the effectiveness of thymectomy can be drawn from the study. The patient in this case report underwent a thymectomy approximately 22 years before presenting to the chiropractor. After the surgery the patient indicated some improvement in ambulation and breathing but still experienced symptoms of the disease. We can only assume that the patient’s condition was not improving after he was diagnosed with the disease and, hence, the decision then to perform a thymectomy. With respect to the thymectomy, Durelli et al26 found in their study groups that those patients without thymoma and not requiring additional immunosuppressive therapy had the highest stable remission rate occurring at 2 years after thymectomy. Those treated
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with immunosuppressive drugs had the highest stable remission rate 5 years after surgery. This patient reported stable remission some 22 years after the thymectomy. Is the patient’s improvement to be credited to the thymectomy after 22 years? We do not believe this is the case. According to Massey,21 “although the onset and extent of improvement are unpredictable with thymectomy, any weakness that is persistent for one year after thymectomy is unlikely to remit.” Arguably, one may say that time alone could account for the recovery of the patient described in this report. By the same token, one may also argue that if the passage of time was the significant clinical difference in this patient, then why did this patient’s condition not improve at 3, 5, 10, or 15 years after diagnosis. Because this is a case report, it is not the purpose of this writing to prove but rather to illustrate a clinical scenario of a chiropractic patient with myasthenia gravis, the patient’s possible response to chiropractic treatment (recovery), as well as a theoretical exposition of the mechanisms of the chiropractic intervention. Another possibility for patient improvement may be due to the specific effects of the treatment applied. Myasthenia gravis is an autoimmune disorder. Chiropractors for the most part adhere to the principle of the “supremacy of the nervous system,” and theories exist with regard to the possible effects of the spinal adjustment on the immune system.27-29 The neurodystrophic hypothesis29 states that neural dysfunction (ie, subluxation) is stressful to visceral and other body structures, resulting in lowered body resistance to disease. This decreased resistance results in modified nonspecific and specific immune responses and alters the trophic function of the involved nerves. Chiropractic theories posit that through spinal adjustments, neural dysfunction may be alleviated or corrected, thereby promoting the body toward wellness in the biologic spectrum of health. What are the anatomic and physiological evidence pointing to a neural-immune interaction? The discussion below provides a sampling to address the above question. Sympathetic noradrenergic innervation of lymphoid organs exists.30 Postganglionic sympathetic axons arborize widely to organs of the immune system and in association with smooth muscle compartments, as well as in the parenchyma, give rise to various sites of release for target cells of the immune system. For example, noradrenergic nerve fibers have revealed extensive networks to the hemopoietic and lymphopoietic cells in the bone marrow.31-33 The functional role of such innervation is provided by Maestroni et al,34 in which syngeneic bone marrow transfer (after chemical sympathectomy) increased peripheral white blood cell count. In secondary lymphoid organs such as the spleen, studies have shown noradrenergic fibers distribute to T lymphocytes and within follicular B cell zones, as well as macrophage zones at the marginal sinus.35-37 This innervation is also observed in the cervical, mesenteric, and popliteal lymph nodes, as well as Peyer’s patches.37-39 Having established a neural connection, how then does autonomic stimulation influence immunologic reactivity? To address this question, let us examine the role of neuropeptides; in particular, the role of
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substance P, somatostatin and the effects of catecholamines. Substance P can induce interleukin-1, tumor necrosis factor, and interleukin-6 production by unstimulated human blood monocytes.39 Substance P has been found to play a role in local and systemic host defense response to inflammation and injury. In vitro studies have demonstrated that both Band T-cell activity can be influenced by substance P.40,41 Human T lymphocyte in vitro proliferation has been shown to be augmented by substance P. Polyclonal immunoglobulin A production in Peyer’s patch and mesenteric lymph nodes in vitro is enhanced by substance P, whereas immunoglobulin M production was not as affected, and immunoglobulin G production was unchanged.42-44 Substance P has also been found to act directly on B cells to induce changes in immunoglobulin secretion.45 In vitro, somatostatin has been found to have inhibitory effects opposite those described for substance P.45-47 Of interest is the suggestion that substance P and somatostatin may mediate isotype- and organ-specific regulation of B-cell differentiation in vitro. There is further suggestion that both may act in concert to regulate the neurophysiological response to influence tissue-specific synthesis of a particular cell isotype. Adrenoreceptors exist on T and B lymphocytes, as well as on neutrophils and macrophages.48-50 They are therefore targets for catecholamine signaling, particularly sympathetic nerve terminal release of norepinephrine. Experimental evidence exists that antibody responses, proliferation, and lytic activity could be reduced, increased, or modified by adrenoreceptor stimulation. Of particular interest are the findings that epinephrine may act directly on lymphocytes to alter antibody response.50-52 The effect of catecholamines is not a simple up- or down-regulation of the immune response but may be dependent on the individual cells involved. Preliminary evidence exists that spinal manipulation may have demonstrable physiological effects suggestive of a neuroendocrine-immune function.53,54 A possible mechanism of the effects of spinal manipulation may work through somatovisceral reflexes.55-57 That is, somatic afferent nerve stimulation via chiropractic adjustments may somehow regulate various visceral responses that are neurologically reflex in nature. This continues to be a controversy in our profession and has important implications to the scope and practice of chiropractic. The exact mechanisms remain to be fully elucidated. However, there is now additional evidence to suggest that somatovisceral reflexes may be a mediator. For example, studies in animals examining somatovisceral reflexes involving immune function exist. In anesthetized rats, pinching the hind paws increased splenic sympathetic efferent nerve activity. Sympathetic splenic efferent nerve activity can decrease the activity of natural killer cells.58 Electrical stimulation of vagal afferents has been shown to increase the release of lymphocytes from the thymus.59 The third possible reason why a patient’s condition may improve is due to nonspecific effects. For example, patient and doctor expectations of treatment efficacy and the quality of their interactions, the doctor’s attention and interest in the patient’s complaints, as well as the reputation, cost, and
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impressiveness in the treatment may contribute to the effectiveness in the management approach of the patient. These nonspecific factors are often referred to as “placebo effects.” Historically, the success of chiropractic care in the treatment of patients with various disorders and concomitant subluxation have often been dismissed by skeptics who attribute the success of treatment to “placebo effects.” Only in recent years have their importance and implications in the treatment of various disorders been appreciated. Especially when alternative therapies, much maligned and dismissed by skeptics in the past, are now more popular and in growing demand by health consumers.60 Turner et al61 reviewed articles pertaining to the placebo effects in English-language articles and books through Medline (1980-1993) and PsychLit (1963-1993) to estimate the importance and implications of placebo effects. It is beyond the scope of this writing to address all the issues involved. However, in brief, Turner et al61 have found that placebo response rates vary and are much higher than the much-quoted one third. Placebo effects have characteristics similar to active medications such as time effect curves and peak, cumulative, and carryover effects. With respect to patient responses, they found that individuals are not consistent in their placebo responses. Anxiety, expectations, and learning are important factors to explain the placebo effect. Turner et al61 emphasize that the patient’s symptoms, illnesses, and their changes over time are a reflection of the complex interactions between the anatomic and neurophysiological processes of the individual, as well as cognitive-behavioral and environmental factors. Such interactions give rise to the burgeoning field of psychoneuroendoimmunology.62,63 Today, much of the literature and clinical practice accepts and places much emphasis on the importance of the placebo effect.64 Kienle et al65 critically examined and questioned the role and existence of the placebo in clinical practice. The authors examined more than 800 works on the subject of the placebo. We encourage the reader to refer to the original article for details of the study. After their analysis they concluded that the widespread data in the literature on the magnitude and frequency of the placebo effect are largely exaggerated, if not altogether false. We bring up this study in the discussion not so much to refute the effects of the placebo but rather to echo the sentiments of the authors. The point is that one should not rule out the possibility that the patient’s self-healing powers are influenced by a variety of nonpharmacologic or nonsurgical approaches and not dismiss other types of therapeutic procedures. In addition, they comment that to credit the success of such procedures merely to “placebo” is inappropriate and may indicate our ignorance and lack of understanding of such treatments. They emphasize that research and attempts at understanding are more appropriate and serve our patients better. We could not agree more.
CONCLUSION In the management of myasthenia gravis, no standard measure of disease severity and no medical treatment approach has been proven efficacious by rigorous, prospective,
controlled studies. The preponderance of evidence certainly links a “connection” between the immune system and the central nervous system beyond a reasonable doubt. The exact mechanisms involved and the role of chiropractic care and its putative effects largely remain unexplored. Although a specific myasthenia gravis osseous structure does not exist per se, chiropractic approaches to case management use signs (ie, biomechanical and postural assessment), palpatory findings, specific range of motion findings, x-ray studies, and symptoms (ie, pain) to determine the spinal level to be adjusted. Patient outcomes are also determined as above. If the patient’s condition does not improve, then subluxation findings are reevaluated, and the patient’s treatments are varied accordingly. Whether such a treatment process or approach brings about healing as a result of specific or nonspecific effects of the treatment or the treatment is merely “riding on the wave” of remission remains to be fully elucidated. The exact mechanisms leading toward disease and the role of spinal adjusting continue to be some of the greatest challenges for our profession. We hope that this case study encourages further investigation into the holistic approach to patient management by chiropractors vis-à-vis specific adjustments of vertebral subluxation.
ACKNOWLEDGEMENT We express our gratitude to our friend and colleague, Dr. Gerald Waagen, PhD, DC, for his constructive comments in the preparation of this manuscript.
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14. Kaminski HJ, Suarez JI, Ruff RL. Neuromuscular junction physiology in myasthenia gravis: isoforms of the acetylcholine receptor in extraocular muscle and the contribution of sodium channels to the safety factor. Neurology 1997; 48(suppl 5):S8-17. 15. Unwin N. Acetylcholine receptor channel imaged in the open state. Nature 1995;373:37-43. 16. Ohno K, Hutchinson DO, Milone ME, et al. Congenital myasthenic syndrome caused by prolonged acetylcholine receptor channel openings due to a mutation in the M2 domain of the subunit. Proc Natl Acad Sci USA 1995;92:758-62. 17. Hopkins LC. Clinical features of myasthenia gravis. Neurol Clin 1994;12:243-61. 18. Drachman DB. Myasthenia gravis. N Engl J Med 1994; 330:1797-807. 19. Garlepp MJ, Kay PH, Dawkins RL. The diagnostic significance of autoantibodies to the acetylcholine receptor. J Neuroimmunol 1982;3:337-50. 20. Kinsella LJ, Lange DJ, Trojaborg W, Sadiq SA, Younger DS, Latov N. Clinical and electrophysiologic correlates of elevated anti-GM1 antibody titers. Neurology 1994;44:1278-82. 21. Massey JM. Treatment of acquired myasthenia gravis. Neurology 1997;48(suppl 5):S46-S51. 22. Araghi J. Juvenile myesthenia gravis: a case study in chiropractic management. Proceedings of the National Conference on Chiropractic and Pediatrics. ICA Council on Chiropractic Pediatrics. Palm Springs, CA; October 1993:122-31. 23. Job analysis in chiropractic Greeley (CO): National Board of Chiropractic Examiners; 1992. 24. Plaugher G, Lopes M, eds. Textbook of clinical chiropractic: a specific biomechanical approach. Baltimore: Williams & Wilkins; 1995. 25. Mayer SA. Intensive care of the myasthenic patient. Neurology 1997;48(Suppl 5):S70-S75. 26. Durelli L, Maggi G, Casadio C, Ferri R, Rendine S, Bergamini L. Actuarial analysis of the occurrence of remissions following thymectomy for myasthenia gravis in 400 patients. J Neurol Neurosurg Psychiatry 1991;54:406-11. 27. Korr IM. Somatic dysfunction, osteopathic manipulative treatment, and the nervous system: a few facts, some theories, many questions. J Am Osteopath Assoc 1986;86:109-14. 28. Greenspan J, Melchior J. The effect of osteopathic manipulative treatment on the resistance of rats to stressful situations. J Am Osteopath Assoc 1966;65:87-91. 29. Leach RA. The chiropractic theories. 2nd ed. Baltimore: Williams & Wilkins; 1986:293-321. 30. Felten DL. Neurotransmitter signaling of cells of the immune system: important progress, major gaps. Brain Behav Immun 1991;5:2-8. 31. Gibson-Berry KL, Whitin JC, Cohen HJ. Modulation of the respiratory burst in human neutrophils by isoproterenol and dibutyryl cyclic AMP. J Neuroimmunol 1993;43:59-68. 32. Calvo W. The innervation of the bone marrow in laboratory animals. Am J Anat 1968;123:315-28. 33. Carlson SL, Brooks WH, Roszman TL. Neurotransmitterlymphocyte interactions; dual receptor modulation of lymphocyte proliferation and cAMP production. J Neuroimmunol 1989;24:155-62. 34. Maestroni GJM, Conti A, Pedrinis E. Efficacy of adrenergic agents on hematopoiesis after syngeneic bone marrow transplantation in mice. Blood 1992;80:1178-82. 35. Felten DL, Livnat S, Felten SY, Carlson SL, Bellinger DL, Yeh P. Sympathetic innervation of lymph nodes in mice. Brain Res Bull 1984;13:693-9. 36. Felten DL, Felten SY, Bellinger DL, Carlson SL, Ackerman KD, Madden KS, et al. Noradrenergic sympathetic neural interactions with the immune system: structure and function. Immunol Rev 1987;100:225-60.
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37. Felten DL, Felten SY, Bellinger DL, Carlson SL, Ackerman KD, Madden KS, et al. Noradrenergic sympathetic innervation of lymphoid organs. Prog Allergy 1988;43:14-36. 38. Felten DL, Felten SY, Carlson SL, Olschowka JA, Livnat S. Noradrenergic and peptidergic innervation of lymphoid tissue. J Immunol 1985;135(suppl):755s-765s. 39. Lotz M, Vaughan JH, Carson DA. Effect of neuropeptides on production of inflammatory cytokines by human monocytes. Science 1988;241(4870):1218-21. 40. Payan DG, Brewster DR, Goetzl EJ. Specific stimulation of human T lymphocytes by substance P. J Immunol 1983; 131:1613-5. 41. Payan DG, Brewster DR, Missirian-Bastian A, Goetzl EJ. Substance P recognition by a subset of human T lymphocytes. J Clin Invest 1984;74:1532-9. 42. Payan DG, Goetzl EJ. Dual roles of substance P: modulator of immune and neuroendocrine functions. Ann N Y Acad Sci 1987;512:465-75. 43. Calvo CF, Chavanel G, Senik A. Substance P enhances IL-2 expression in activated human T cells. J Immunol 1992; 148:3498-504. 44. Stanisz AM, Befus D, Bienenstock J. Differential effects of vasoactive intestinal peptide, substance P, and somatostatin on immunoglobulin synthesis and proliferations by lymphocytes from Peyer’s patches, mesenteric lymph nodes, and spleen. J Immunol 1986;136:152-6. 45. Pascual DW, Xu-Amano JC, Kiyono H, McGhee JR, Bost KL. Substance P acts directly upon cloned B lymphoma cells to enhance IgA and IgM production. J Immunol 1991; 146:2130-6. 46. Malec P, Zeman K, Markiewicz K, Tchorzewski H, Nowak Z, Baj Z. Short-term somatostatin infusion affects T lymphocyte responsiveness in humans. Immunopharmacology 1989; 17:45-9. 47. Muscettola M, Grasso G. Somatostatin and vasoactive intestinal peptide reduce interferon gamma production by human peripheral blood mononuclear cells. Immunobiology 1990; 180:419-30. 48. Li YS, Kouassi E, Revillard JP. Differential regulation of mouse B-cell activation by beta-adrenoceptor stimulation depending on type of mitogens. Immunology 1990;69:367-72. 49. Motulsky HJ, Insel PA. Adrenergic receptors in man: direct identification, physiologic regulation, and clinical alterations. N Engl J Med 1982;307:18-29. 50. Infante JR, Peran F, Martinez M, Poyatos R, Roldan A, Ruiz C, et al. Lymphocyte subpopulations and catecholamines; daytime variations and relationships. Rev Esp Fisiol 1996;52:143-8. 51. Elenkov IJ, Papanicolaou DA, Wilder RL, Chrousos GP. Modulatory effects of glucocorticoids and catecholamines on human interleukin-12 and interleukin-10 production: clinical implications. Proc Assoc Am Physicians 1996;108:374-81. 52. Felsner P, Hofer D, Rinner I, Mangge H, Gruber M, Korsatko W, et al. Continuous in vivo treatment with catecholamines suppresses in vitro reactivity of rat peripheral blood. T-lymphocytes via alpha-mediated mechanisms. J Neuroimmunol 1992;37:47-57. 53. Brennan PC, Kokjohn K, Kaltinger CJ, Lohr GE, Glendening C, Hondras MA, et al. Enhanced phagocytic cell respiratory burst induced by spinal manipulation: potential role of substance P. J Manipulative Physiol Ther 1991;14:399-408. 54. Brennan PC, Triano JJ, McGregor M, Kokjohn K, Hondras MA, Brennan DC. Enhanced neutrophil respiratory burst as a biological marker for manipulation forces: duration of the effect and association with substance P and tumor necrosis factor. J Manipulative Physiol Ther 1992;15:83-9. 55. Sato A. Neural mechanisms of autonomic responses elicited by somatic sensory stimulation. Neurosci Behav Physiol 1997; 27:610-20.
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56. Budgell B, Sato A. Modulation of autonomic function by somatic nociceptive inputs. Prog Brain Res 1996;113:525-39. 57. Alcantara J. Neurology in somatovisceral aspects: a chiropractic approach. Masarsky C, Masarsky M. eds. Baltimore: Lippincott-Raven. 58. Kimura A, Nanai N, Sato A. Somatic afferent regulation of cytotoxic activity of splenic natural killer cells in anesthetized rats. Jpn J Physiol 1994;44:651-64. 59. Antonica A, Magni F, Mearini L, Paolocci N. Vagal control of lymphocyte release from rat thymus. J Auton Nerv Sys 1994;48:187-97. 60. Eisenberg DM, Kessler RC, Foster C, Norlock FE, Calkins DR, Delbanco TL. Unconventional medicine in the United States. Prevalence, costs, and patterns of use. N Engl J Med 1993;328:246-52.
61. Turner JA, Deyo RA, Loeser JD, Korff MV, Fordyce WE. The importance of placebo effects in pain treatment and research. JAMA 1994;271:1609-14. 62. Moynihan JA, Ader R. Psychoneuroimmunology: animal models of disease. Psychosom Med 1996;58:546-58. 63. Sheridan JF, Dobbs C, Brown D, Zwilling B. Psychoneuroimmunology: stress effects on pathogenesis and immunity during infection. Clin Microbiol Rev 1994;7:200-12. 64. Jamison JR. Psychoneuroendoimmunology: the biological basis of the placebo phenomenon? J Manipulative Physiol Ther 1996;19:484-7. 65. Kienle GS, Kiene H. Placebo effect and placebo concept: a critical methodological and conceptual analysis of reports on the magnitude of the placebo effect. Alternative Ther 1996;2:39-54.
CASE REPORTS Chiropractic Management of a Patient with Myasthenia Gravis and Vertebral Subluxations Joel Alcantara, DC,a David M. Steiner, DC,b Gregory Plaugher, DC,c and Joey Alcantarad
ABSTRACT Objective: The chiropractic management of a patient with myasthenia gravis and vertebral subluxation is described. We discuss the pathophysiology, clinical features, and treatment of patients with these diseases. Clinical Features: The 63-year-old male patient suffered from complaints associated with the disease myasthenia gravis along with signs of vertebral subluxation. The patient had an initial complaint of dysphagia. In addition, the patient experienced swelling of the tongue, nausea, digestive problems, weakness in the eye muscles, difficulty breathing, myopia, diplopia, and headaches. Balance and coordination problems resulted in walking difficulties.
INTRODUCTION The English physician Thomas Willis first described the clinical syndrome of myasthenia gravis in 1672.1 In 1895 Jolly named the disease, “myasthenia gravis pseudoparalytica.”2 In the Americas in the 1600s, the Indian chief Opechankanough may have been the first American identified with the disease.3 According to a 1994 estimate, approximately 36,415 patients have myasthenia gravis in the United States, and the number of people in whom myasthenia gravis will develop is estimated at 1014 per year.4,5 Myasthenia gravis is an autoimmune disorder with patient complaints of voluntary muscle weakness. The distribution of weakness may involve the ocular, facial, oropharyngeal,
a Assistant Professor, Palmer College of Chiropractic West, San Jose, California, and Research Associate, Gonstead Clinical Studies Society, Mt. Horeb, Wisconsin. b Private Practice of Chiropractic, Miramar, Florida c Associate Professor, Life Chiropractic College West, San Lorenzo, California, and Director of Research, Gonstead Clinical Studies Society, Mt. Horeb, Wisconsin. d Chiropractic Intern, Palmer College of Chiropractic West and Professional Member, Association of Professional Engineers, Geologists and Geophysicists of Alberta (APEGGA), Canada. Submit reprint requests to: Joel Alcantara, BSc, DC, Palmer Center for Chiropractic Research, Palmer College of Chiropractic-West, 90 E Tasman Dr, San Jose, CA 95134; [email protected]. Paper submitted April 27, 1998; in revised form May 18, 1998. Funded by Palmer College of Chiropractic West, San Jose, California and the Gonstead Clinical Studies Society, Mount Horeb, Wisconsin.
Intervention and Outcome: Contact specific, highvelocity, low-amplitude adjustments were applied to sites of patient subluxation. Myasthenia gravis is no longer debilitating to the patient; he is medication free and has resumed a “normal life.” Conclusion: The clinical aspects of the disease, including the possible role of chiropractic intervention in the treatment of patients suffering from myasthenia gravis, are also discussed. This case study encourages further investigation into the holistic approach to patient management by chiropractors vis-à-vis specific adjustments of vertebral subluxation. (J Manipulative Physiol Ther 1999;22:333-40) Key Indexing Terms: Myasthenia Gravis; Chiropractic; Dysphagia
and limb muscles. Not surprisingly, the cranial nerves are almost invariably involved, in particular cranial nerves III, IV, VI, and VII. Most patients therefore have ptosis, diplopia, dysarthria, and dysphagia. The weakness has characteristic features of fluctuations and variability leading to perceptible exacerbations and remissions.6,7 Sensory deficits of any consequence are rare and may be attributable to concomitant disorders such as diabetic neuropathy or rheumatoid arthritis. Diagnosis is confirmed by the unequivocal and reproducible improvement after intravenous administration of the rapidly acting anticholinesterase drug, edrophonium chloride, otherwise known as Tensilon.8 We report on the chiropractic management of a patient with myasthenia gravis and discuss the relevant clinical features of the disease, including the possible role of chiropractic intervention(s).
CASE REPORT On June 23, 1996, a 63-year-old man sought care, complaining of signs and symptoms related to myasthenia gravis. He had suffered from this disease for approximately 30 years. His reason for this visit was an inability to swallow. The patient related that he would often have to massage his throat for the food to move down his esophagus. He described feeling as if he was going to choke to death. In addition, he experienced swelling of the tongue, weakness in the eye muscles, difficulty breathing, diplopia, myopia, digestive problems, nausea, and headaches. He also reported walking difficulties resulting from problems with balance and coordination. In 1975, 6 years after being diagnosed with myasthenia gravis, the patient underwent a thymecto-
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Fig 1. Radiographic study demonstrates the lateral view of the cervical spine.
my. Before the surgery, the patient was wheelchair bound because of muscle weakness and motor control problems. After the thymectomy he became ambulatory once again, and his breathing improved. Medical management before chiropractic consultation included plans of placing him in an iron lung because of breathing difficulties. At the time of chiropractic consultation, the patient was taking the prescription drug pyridostigmine (Mestinon) 3 to 4 times per day. In spite of the medication, the patient would still experience the above-mentioned signs and symptoms. Physical examination findings noted the following. His shoulder height was higher on the left. His left hip (gluteus maximus) appeared to be narrower than his right. Temposcope skin temperature differentials were noted at the C7 and T4 spinal levels. Motion palpation findings at these levels showed restrictions. Edema, muscular hypertonicity, and tenderness to palpation were also notable at the C7 and T4 area. Full-spine radiographs were obtained. The lateral radiographs reveal a loss of the cervical lordosis (Fig 1). Spondylosis was noted predominately at the C5/C6 vertebral levels, with the C5/C6 and C6/C7 disc spaces diminished. In addition, osteophyte formations were notable mainly at the anterior end plates of the C5 and C6 spinal levels. The C7 vertebral body was noted to be in an extension malposition, with the disc space wider at the anterior and
narrower at the posterior. The patient’s lumbopelvic lateral radiograph demonstrated hypolordosis (Fig 2). The anteroposterior view revealed a pelvic tilt to the left in part because of a 7-mm left femoral head-height deficiency. The obturator foramen on the right appeared to be narrower, and on the left it appeared wider. This is indicative of rotation in the pelvis (ie, external rotation of the left ilium). There appeared to be a tilting of the spine starting at the patient’s mid to upper back, probably because of a lateral flexion misalignment at the T4 vertebral level. There appeared to be a welldelineated calcified lesion posterior to the C6 and C7 spinous processes indicating a possible old spinal injury. The primary subluxation adjusted were predominately located at the C7 and T4 spinal levels. On occasion the patient presented to the treating chiropractor complaining of hip pain. An adjustment to his pelvis on the basis of subluxation findings would be applied, resulting in a favorable outcome. After a total of 33 visits, the patient was instructed to come in once or twice a month or on an “as-needed” basis. The patient continued to visit the treating chiropractor on a regular basis. During the course of a year, the patient had flare-ups and needed to be seen more frequently. The flare-ups consisted primarily of complaints of weakness in his left eye. His left eyelid became weak and drooped, interfering with proper vision, as well as producing diplopia. On January 29, 1997, the patient presented for treatment with his left eye closed. He stated that it had been that way for the past week and seemed to be getting worse. After five adjustments in 5 visits, the patient reported that his left eyelid had started to open up since the five treatments began. By April 11, 1997 (or after 12 adjustments), he indicated further improvement in his left eye complaint. By May 16, 1997 (or 13 visits), he related that his left eye was “perfect” and that it remained open continuously. The patient denied weakness in the left eye muscles; there was an absence of droopiness in the eyelid, and the diplopia was no longer present. The patient indicated that he started to notice improvement within the first 2 weeks of care, and as treatment continued, he felt better and better, eventually being weaned off his medication. During the course of his treatment by the chiropractor, the patient was also monitored by his medical doctor. The patient continues to be medication free. Even with the exacerbation of his left eye, he was able to overcome it exclusively by receiving adjustments to the cervical spine. His last visit to the treating chiropractor was on June 24, 1997. At that time, the patient reported that he was not experiencing any signs or symptoms of myasthenia gravis. When he first presented to the treating chiropractor, the patient was semiretired and working with no regularity. Presently, he is working full-time as a businessman.
DISCUSSION Pathophysiology Myasthenia gravis is an autoimmune disorder that affects the skeletal muscles. The pathophysiology of the disease involves the presynaptic nerve terminal and structures locat-
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Fig 3. Radiographic study demonstrating the anteroposterior view of the lumbopelvis.
Fig 2. Radiographic study demonstrates the lateral view of the lumbopelvis.
ed in the postsynaptic skeletal muscle membrane. In a simplistic approach, we provide the following description of the disease. For a more extensive discussion on the topic, we refer the reader elsewhere.9-11 Calcium entry into the nerve terminal at a neuromuscular junction triggers the release of acetylcholine (ACh) from storage vesicles within the nerve terminal.12 Each synaptic vesicle releases about 10,000 ACh molecules into the synaptic cleft,13 where it diffuses rapidly throughout. At the postsynaptic membrane, acetylcholine receptors (AChR) line the primary synaptic clefts. The membrane itself contains depressions resulting from membrane in-folding to increase membrane surface area. The AChR is a transmembrane glycoprotein structure composed of 5 subunits that is cation-selective and ligand gated.14 In a possible ligand-receptor interaction put forth, the binding of ACh may somehow cause the AChR subunits to move and portions of the transmembrane protein may form a gate that opens.14 Opening of these gates is a requisite for ion permeability, membrane depolarization, and a resultant action potential for muscle contraction. In myasthenia gravis antibodies generated by the immune system attack the AChR. The resultant antibody-receptor structure may result in receptor blockade. The main immunogenic regions are
located close to but distinct from the subunit of the AChR.14,15 Another possibility from an antibody-receptor interaction perspective is that the AChR structure may be altered, resulting in poor affinity of the ACh for the receptor. The resultant size or duration of a single channel current because of the ion permeability or the duration of opening burst of the receptor gates may thus be affected.14,16 Overall, regardless of the specific effect of AChR binding by antibodies, the result is an inadequate response to ACh release and therefore muscle response.
Diagnosis Myasthenia gravis is a common disease of the neuromuscular junction and is considered fairly stereotypical. For example, most patients have ptosis, ophthalmoplegia, dysarthria, and dysphagia. Myasthenia gravis is known as the “great imitator” because it may mimic cranial nerve palsies and brainstem diseases, myopathies, and anterior horn cell disease.17 It is beyond the scope of this writing to delve into great detail with respect to diagnosis, and the reader is referred elsewhere.18 The demonstration of weakness with continued use and improvement in strength with a short rest is diagnostic. The patient may be referred to a medical doctor for the Tensilon test, which is readily available. However, some caveats are worth mentioning, because this test has associated risks. The drug may be dangerous and life threatening, particularly to the elderly, those with
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heart disease, and individuals with obstructive lung disease. Also the test may be difficult to interpret and difficult to tell from placebo, especially when the complaint of weakness is mild.17 Immunologic testing for the AChR is very reliable. However, false-positive results may occur in some patients, such as those with systemic lupus erythematosus.19 Finally, electrophysiological testing may also be performed, and the reader is referred elsewhere for a more complete discussion20 on the topic.
Medical Treatment The goal of any treatment regimen, medical or otherwise, is to produce normal function. The ideal therapy should have rapid onset with minimal side effects, be easy to administer, and have low cost. The following is a cursory overview of some of the medical approaches to the disease, based on the work by Massey.21 Cholinesterase inhibitors are usually used as the initial therapy. They provide symptomatic improvement for a time by hindering the hydrolysis of acetylcholine at the neuromuscular junction. However, this approach alone is rarely sufficient. Pyridostigmine bromide (Mestinone) and neostigmine bromide (Prostigmine) are the most commonly used agents. Common side effects are gastrointestinal hyperactivity and increased upper and respiratory secretions, as well as bradycardia. Thymectomy is another approach to treatment, although no prospective blinded study has ever been performed nor is the association between the thymus and the pathogenesis of myasthenia gravis fully understood. There are reports that more than 50% of patients undergoing thymectomy experience sustained improvement. The use of immunosuppressant drugs is another treatment choice. However, because of the increased risk of infection as a result of the immunosuppression, as well as the potential side effects of the individual drugs, this route of care must be used with caution. The treatment is dependent on the rate of progression and the severity of weakness in patients’ symptoms and the potential side effects of the medication. Immunosuppressant agents used are corticosteroids, azathioprine, cyclosporine, and cyclophosphamide. Other forms of therapy include plasmapheresis, intravenous immunoglobulin, total body radiation, splenectomy, thoracic duct lymph drainage, and anti-thymocyte globulin.
Chiropractic Care This is the second citation in the scientific literature describing the chiropractic management of a patient with myasthenia gravis. Araghi22 reported in a conference proceedings the chiropractic care of a 2-year-old female patient in whom myasthenia gravis developed after a motor vehicle collision. She had the following symptoms after injury: otitis media, ptosis of the right eye (developed 8 days after trauma), lethargy, lower extremity weakness, bilateral toe-in foot flare, and a moderate left head tilt. The patient had a positive Tensilon test result and electromyogram. The patient was adjusted at S2, atlas, and occiput, with the Gonstead technique. Her symptoms were nearly completely
resolved after 5 months of care. The patient presented in this case report was also managed with the Gonstead technique. The technique is an established method of patient management and is highly used within the practice of chiropractic.23 The management approach with respect to examination findings (ie, inspection, palpation, range of motion, spinography and x-ray marking, and Nervoscope instrumentation) and treatment approach (ie, adjustments with respect to patient position, doctor’s stance, patient and doctor’s contact point, line of drive, line of correction, and torque) are well described in the Gonstead reference text by Plaugher and Lopes.24 The patient was treated during a total of 80 visits over a period of approximately 2 years. The main subluxation findings were at C7 PLS, T4 PRI-T, and L5 PL. To delineate the possible role of chiropractic intervention in the treatment of patients suffering from a myriad of conditions, we will examine the effects of treatment from three possible perspectives with respect to patient improvement. One reason why a patient’s condition may improve is due to the natural history of the disease or regression to the mean. That is, regardless of the treatment the patient may receive, the patient’s problems resolve. Regression to the mean refers to the phenomenon in which the patient’s symptoms are to the extreme on first examination and then return to their more natural or typical state, which are not so severe. According to Massey,21 because of 22% of untreated patients achieving remission and another 18% experiencing marked improvement, it is difficult to sort out the effects of any therapeutic improvement on myasthenia gravis from the natural history of the disease. The role of the natural history of this disease is confounded by the patient’s thymectomy some 6 years after being diagnosed with the disease if one is of the opinion that 6 years is not ample time to decide that the disease will not improve. In addition, approximately 30% of patients with myasthenia gravis will experience weakness in the respiratory muscles, and approximately 15% to 20% will experience myasthenia crisis. Myasthenia crisis is defined as respiratory failure requiring mechanical ventilation.25 A study by Durelli et al26 examined the occurrence of remissions in 400 patients who had myasthenia gravis with thymectomy. These patients had an overall stable remission of 27%. Incidentally, Durelli et al26 caution that, in the absence of a concurrent control group of nonthymectomized patients, no definitive conclusions about the effectiveness of thymectomy can be drawn from the study. The patient in this case report underwent a thymectomy approximately 22 years before presenting to the chiropractor. After the surgery the patient indicated some improvement in ambulation and breathing but still experienced symptoms of the disease. We can only assume that the patient’s condition was not improving after he was diagnosed with the disease and, hence, the decision then to perform a thymectomy. With respect to the thymectomy, Durelli et al26 found in their study groups that those patients without thymoma and not requiring additional immunosuppressive therapy had the highest stable remission rate occurring at 2 years after thymectomy. Those treated
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with immunosuppressive drugs had the highest stable remission rate 5 years after surgery. This patient reported stable remission some 22 years after the thymectomy. Is the patient’s improvement to be credited to the thymectomy after 22 years? We do not believe this is the case. According to Massey,21 “although the onset and extent of improvement are unpredictable with thymectomy, any weakness that is persistent for one year after thymectomy is unlikely to remit.” Arguably, one may say that time alone could account for the recovery of the patient described in this report. By the same token, one may also argue that if the passage of time was the significant clinical difference in this patient, then why did this patient’s condition not improve at 3, 5, 10, or 15 years after diagnosis. Because this is a case report, it is not the purpose of this writing to prove but rather to illustrate a clinical scenario of a chiropractic patient with myasthenia gravis, the patient’s possible response to chiropractic treatment (recovery), as well as a theoretical exposition of the mechanisms of the chiropractic intervention. Another possibility for patient improvement may be due to the specific effects of the treatment applied. Myasthenia gravis is an autoimmune disorder. Chiropractors for the most part adhere to the principle of the “supremacy of the nervous system,” and theories exist with regard to the possible effects of the spinal adjustment on the immune system.27-29 The neurodystrophic hypothesis29 states that neural dysfunction (ie, subluxation) is stressful to visceral and other body structures, resulting in lowered body resistance to disease. This decreased resistance results in modified nonspecific and specific immune responses and alters the trophic function of the involved nerves. Chiropractic theories posit that through spinal adjustments, neural dysfunction may be alleviated or corrected, thereby promoting the body toward wellness in the biologic spectrum of health. What are the anatomic and physiological evidence pointing to a neural-immune interaction? The discussion below provides a sampling to address the above question. Sympathetic noradrenergic innervation of lymphoid organs exists.30 Postganglionic sympathetic axons arborize widely to organs of the immune system and in association with smooth muscle compartments, as well as in the parenchyma, give rise to various sites of release for target cells of the immune system. For example, noradrenergic nerve fibers have revealed extensive networks to the hemopoietic and lymphopoietic cells in the bone marrow.31-33 The functional role of such innervation is provided by Maestroni et al,34 in which syngeneic bone marrow transfer (after chemical sympathectomy) increased peripheral white blood cell count. In secondary lymphoid organs such as the spleen, studies have shown noradrenergic fibers distribute to T lymphocytes and within follicular B cell zones, as well as macrophage zones at the marginal sinus.35-37 This innervation is also observed in the cervical, mesenteric, and popliteal lymph nodes, as well as Peyer’s patches.37-39 Having established a neural connection, how then does autonomic stimulation influence immunologic reactivity? To address this question, let us examine the role of neuropeptides; in particular, the role of
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substance P, somatostatin and the effects of catecholamines. Substance P can induce interleukin-1, tumor necrosis factor, and interleukin-6 production by unstimulated human blood monocytes.39 Substance P has been found to play a role in local and systemic host defense response to inflammation and injury. In vitro studies have demonstrated that both Band T-cell activity can be influenced by substance P.40,41 Human T lymphocyte in vitro proliferation has been shown to be augmented by substance P. Polyclonal immunoglobulin A production in Peyer’s patch and mesenteric lymph nodes in vitro is enhanced by substance P, whereas immunoglobulin M production was not as affected, and immunoglobulin G production was unchanged.42-44 Substance P has also been found to act directly on B cells to induce changes in immunoglobulin secretion.45 In vitro, somatostatin has been found to have inhibitory effects opposite those described for substance P.45-47 Of interest is the suggestion that substance P and somatostatin may mediate isotype- and organ-specific regulation of B-cell differentiation in vitro. There is further suggestion that both may act in concert to regulate the neurophysiological response to influence tissue-specific synthesis of a particular cell isotype. Adrenoreceptors exist on T and B lymphocytes, as well as on neutrophils and macrophages.48-50 They are therefore targets for catecholamine signaling, particularly sympathetic nerve terminal release of norepinephrine. Experimental evidence exists that antibody responses, proliferation, and lytic activity could be reduced, increased, or modified by adrenoreceptor stimulation. Of particular interest are the findings that epinephrine may act directly on lymphocytes to alter antibody response.50-52 The effect of catecholamines is not a simple up- or down-regulation of the immune response but may be dependent on the individual cells involved. Preliminary evidence exists that spinal manipulation may have demonstrable physiological effects suggestive of a neuroendocrine-immune function.53,54 A possible mechanism of the effects of spinal manipulation may work through somatovisceral reflexes.55-57 That is, somatic afferent nerve stimulation via chiropractic adjustments may somehow regulate various visceral responses that are neurologically reflex in nature. This continues to be a controversy in our profession and has important implications to the scope and practice of chiropractic. The exact mechanisms remain to be fully elucidated. However, there is now additional evidence to suggest that somatovisceral reflexes may be a mediator. For example, studies in animals examining somatovisceral reflexes involving immune function exist. In anesthetized rats, pinching the hind paws increased splenic sympathetic efferent nerve activity. Sympathetic splenic efferent nerve activity can decrease the activity of natural killer cells.58 Electrical stimulation of vagal afferents has been shown to increase the release of lymphocytes from the thymus.59 The third possible reason why a patient’s condition may improve is due to nonspecific effects. For example, patient and doctor expectations of treatment efficacy and the quality of their interactions, the doctor’s attention and interest in the patient’s complaints, as well as the reputation, cost, and
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impressiveness in the treatment may contribute to the effectiveness in the management approach of the patient. These nonspecific factors are often referred to as “placebo effects.” Historically, the success of chiropractic care in the treatment of patients with various disorders and concomitant subluxation have often been dismissed by skeptics who attribute the success of treatment to “placebo effects.” Only in recent years have their importance and implications in the treatment of various disorders been appreciated. Especially when alternative therapies, much maligned and dismissed by skeptics in the past, are now more popular and in growing demand by health consumers.60 Turner et al61 reviewed articles pertaining to the placebo effects in English-language articles and books through Medline (1980-1993) and PsychLit (1963-1993) to estimate the importance and implications of placebo effects. It is beyond the scope of this writing to address all the issues involved. However, in brief, Turner et al61 have found that placebo response rates vary and are much higher than the much-quoted one third. Placebo effects have characteristics similar to active medications such as time effect curves and peak, cumulative, and carryover effects. With respect to patient responses, they found that individuals are not consistent in their placebo responses. Anxiety, expectations, and learning are important factors to explain the placebo effect. Turner et al61 emphasize that the patient’s symptoms, illnesses, and their changes over time are a reflection of the complex interactions between the anatomic and neurophysiological processes of the individual, as well as cognitive-behavioral and environmental factors. Such interactions give rise to the burgeoning field of psychoneuroendoimmunology.62,63 Today, much of the literature and clinical practice accepts and places much emphasis on the importance of the placebo effect.64 Kienle et al65 critically examined and questioned the role and existence of the placebo in clinical practice. The authors examined more than 800 works on the subject of the placebo. We encourage the reader to refer to the original article for details of the study. After their analysis they concluded that the widespread data in the literature on the magnitude and frequency of the placebo effect are largely exaggerated, if not altogether false. We bring up this study in the discussion not so much to refute the effects of the placebo but rather to echo the sentiments of the authors. The point is that one should not rule out the possibility that the patient’s self-healing powers are influenced by a variety of nonpharmacologic or nonsurgical approaches and not dismiss other types of therapeutic procedures. In addition, they comment that to credit the success of such procedures merely to “placebo” is inappropriate and may indicate our ignorance and lack of understanding of such treatments. They emphasize that research and attempts at understanding are more appropriate and serve our patients better. We could not agree more.
CONCLUSION In the management of myasthenia gravis, no standard measure of disease severity and no medical treatment approach has been proven efficacious by rigorous, prospective,
controlled studies. The preponderance of evidence certainly links a “connection” between the immune system and the central nervous system beyond a reasonable doubt. The exact mechanisms involved and the role of chiropractic care and its putative effects largely remain unexplored. Although a specific myasthenia gravis osseous structure does not exist per se, chiropractic approaches to case management use signs (ie, biomechanical and postural assessment), palpatory findings, specific range of motion findings, x-ray studies, and symptoms (ie, pain) to determine the spinal level to be adjusted. Patient outcomes are also determined as above. If the patient’s condition does not improve, then subluxation findings are reevaluated, and the patient’s treatments are varied accordingly. Whether such a treatment process or approach brings about healing as a result of specific or nonspecific effects of the treatment or the treatment is merely “riding on the wave” of remission remains to be fully elucidated. The exact mechanisms leading toward disease and the role of spinal adjusting continue to be some of the greatest challenges for our profession. We hope that this case study encourages further investigation into the holistic approach to patient management by chiropractors vis-à-vis specific adjustments of vertebral subluxation.
ACKNOWLEDGEMENT We express our gratitude to our friend and colleague, Dr. Gerald Waagen, PhD, DC, for his constructive comments in the preparation of this manuscript.
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