Palliative treatment of motor neuron disease RICHARD ALAN SMITH, ELLEN GILLIE and JONATHAN LICHT Center for Neurologic Study, San Diego, CA, U.S.A. Advances in the basic sciences make it certain the will to use it in support of the disabled is that the cause of motor neuron disease (MND) not thought extraordinary. Both patients' and will be understood and that a cure will be physicians' attitudes towards prolongation of forthcoming. Sadly for those affected, no therapy useful life has been transformed as a result of currently available can arrest or modify the emphasis on the abilities rather than the disabili- course of this dreaded disease. In short, MND ties of the handicapped (Smith 1987). While it remains one or the last scourges of humankind, has been argued that society may need to ration not to have materially benefited from the medical medical resources as a matter of efficiency there and scientific progress which has characterized is almost universal agreement that these consider- the twentieth century. In spite of this rather ations are not germane in the context of the discouraging picture, the lives of individual pa- physician-patient relationship (Fried 1975). At tients have been enormously improved as a result this level of discussion the decision making of progress in patient care (Norris et al. process is rightfully shifting toward the patient 1985). Persons are now living and even working at the expense of physician. This has had the with MND for years as a result of medical effect of empowering patients - the consequence interventions which support basic bodily func- being that patients are now on a more equal tions and technological innovations which pro- footing with their care providers than they have vide for higher human needs such as been in the past (Cassel 1980). communication. For some curious reasons, patients with MND A number of important social factors have are invariably persons one would cherish as coalesced to bring us to this level of care. On the friends or family. As a group they make few technical side, miniaturization has reduced the demands on physicians who are committed to size of components which has favorably influ- their care but they, like many persons with enced not only the cost, but the reliability and untreatable, chronic disease, resent caretakers transportability of medical devices. Use of a who are indifferent or callous. As a rule MND respirator, for example, no longer brings to mind patients have strong family ties. Recognizing this confinement in an iron lung. Patients on ventila- it is well advised to think of care in the context tors are now free to move about their communi- of the home. This necessitates involving family ties, and travel to distant places is possible. In members as partners. Physicians may be humbled addition to the availability of new technology, in this role since lay persons are often adept at picking up nuances of care that may be unfamiliar specific recommendations that need to be touched to trained professionals. upon. Many of these may reflect biases since In general MND patients enjoy relatively they are often based on common sense or sound health in contrast to numerous other experience rather than medical fact, but they are diseases which threaten multiple systems, leading nonetheless important. Patients with incurable to organ failure, opportunistic infections, etc. illness understandably want to know whether Accordingly the health needs of patients with rlctors such as mental attitude, nutrition, exer- advanced MND may be relatively modest, allow- cise, or physical therapy will favorably influence ing patients to live out their lives at home except the course of their disease. Although the impact on brief occasions when they require hospital of these is uncertain, it cannot be excluded that care. This distinguishes MND from kidney fail- non-specific factors may account for the long- ure, for example, which requires weekly medical term survival of some MND patients (Mulder visits for dialysis or AIDS which is associated and Howard 1976). There are patients who live with a variety of complications and necessitates with the disease for years, possibly because they frequent or prolonged hospitalization. Although have altered their lifestyle in some significant not always feasible. home care is able to meet way. the daily needs of MND patients even when the Although one should avoid endorsement of a disease is far advanced (Norris et a]. 1987b). particular belief system, it is reasonable to suggest For the physician and care providers who that mental attitude may influence the course of assume responsibility for MND patients it is MND. Through discourse, reading or religious Practice patients should be encouraged to explore important to organize a treatment plan in a their resolve to live. More tangible recommends systematic manner. To the degree possible it is tions regarding activities of daily life are welcome. essential to familiarize the patient and family with the treatment strategy. This requires an Considering that there may be a dietary link to ongoing relationship which can take various MND, patients should review their eating habits forms. During an office visit it is necessary to set (Spencer et al. 1987). Our own biases are towards aside enough time to establish meaningful inter- a varied, high fiber, natural diet modestly supple- mented with vitamins. At the minimum this action. Unfortunately the economics of medical dietary recommendation may favorably influence practice often intrude on this goal. Discounting elimination which is coi-nmonly a problem. Con- this factor, it is certain that some physicians are more suite Id than others to the task of caring for sumption of highly processed, canned, artificially flavored and colored food is discouraged, but the chronically ill (Gould 1980). Sensing this, there is no perfect diet and in some areas and in some patients actively search out a compassionate some seasons strict adherence to these principles caregiver, often consulting with a number of would be unrealistic due to expense or availability medical doctors at the onset of their illness until of fresh food stuffs. As for daily activities a they find someone who is willing to make a regular program of exercise is recommended commitment to them. Specialized centers have although patients are advised to avoid fatigue. been developed in association with some hospitals Heat and massage may help alleviate cramps (Hudson 1987). These take a multidisciplinary and muscular spasms. Although these and similar approach to care. In addition to medical services recommendations are not proven to be beneficial, these centers often distribute educational materi- at the minimum they provide comfort. In an age als and sponsor support groups which can Put of computers and transplants we should not patients and family in touch with others who forget the possible therapeutic benefit of simple constitute a network of persons with kindred measures. interests. Once the diagnosis of MND has been estab- MENTATION AND MOOD lished, emphasis for the patient switches to symptomatic and possibly experimental treat- In interaction with MND patients most observers ment. At the outset there are a number of non- have the impression that they are stoical in attitude and generally in control of their circum- son with matched controls (Gallassi et al. 1985). stances, After study of a small group of patients This took the form of impaired reasoning, and it was concluded that this seemingly healthy abstraction and interference with planning and adjustment was attained through the exercise of organization. Recall appeared to be spared. denial of depression and anxiety (Brown and Another study comparing MND patients with a Mueller 1970). Carrying this further it was matched control group consisting of persons with suggested that there might be a premorbid MND non-dementing disease of the nervous system, personality which had etiologic implications. For- failed to confirm these conclusions upholding the tunately, these assumptions have been challenged general impression that cognitive processes are by several investigators. On a standard measure spared in MND except in exceptional instances of personality (MMPI), MND patients were (Poloni et al. 1986). When dementia is associated similar to persons with general medical illnesses with MND it is usually less severe than that (Peters et al. 1978). Studying a group of 40 associated with Aizheimer's disease. This might patients, Houpt et al. concluded that the person- be expected from the pathology which, except ality profile of MND patients was comparable to for patients from the Western Pacific, is usually persons with other serious illnesses (Houpt et al. not associated with neurofibrillary change (Hud- 1977). Using one test parameter, 32.5% of son 1987). When patients are linguistically or persons with MND were moderately depressed. cognitively impaired this adds further hardship Only 2.5% were severely so. A small percentage to an already difficult situation, (10%) exhibited evidence for endogenous depres- sion, suggesting that they might respond to drug SPEECH therapy. Although not unique to MND, pathotogic Depending on the mode of onset speech may be laughter or tearfulness is almost pathognomonic involved early or late in the course of MND. for the disease. This may be exaggerated in some When it is lost it is one of the cruelest conse- instances to the point of embarrassment. Con- quences of the disease. Under normal circum- sidering that any behavioral idiosyncrasy is apt stances speech is made possible as a result of the to impugn one's mental competence it is well modulation of air by the coordinated action of advised to explain the basis for these symptoms the vocal cords, palate, tonguc, and lips which to the patient and their acquaintances. The can be thought of as a series of musculoskeletal pathologic substrate for this behavior is generally valves. As a consequence of weakness and spastic- assumed to result from bilateral involvement of ity, MND patients typically demonstrate a mixed corticobulbar pathways which is common in dysarthria which is characterized by flaccid and MND (Schiffer et al. 1985). The emotional spastic elements (Darley et al. 1969). With lability which results from loss of cortical inhibi- spasticity, hyperadduction of the vocal cords can tion of the brainstem can be thought of as an result causing elevated laryngeal resistance to example of a disconnection syndrome. On empiri- exhalation, and a characteristic asperity of voice. cal grounds treatment with amitriptyline or levo- Weakness of one or both vocal cords, rare in dopa can be considered (Udaka et al. 1984, MND, gives speech a breathy character associ- Schiffer et al. 1985). These therapies have been ated with inhalatory stridor. Although vocal reported to be effective in persons with cerebro- characteristics may vary depending on when in vascular disease and multiple sclerosis and anec- the course of the disease the patient is examined, dotally in MND. typically patients with motor neuron disease While isolated examples of dementia in associa- exhibit hypernasality of speech due to escape of tion with MND have long been recognized, it is air into the nasal pharynx and difficulty in the only recently that attention has focused on the pronunciation of consonants (Aronson 1980). impact of the disease on cognition. As a group Further, vocalization is usually strained, slow in Gallassi and his colleagues found slight cognitive rate, and even in pitch. impairment in a group of 22 patients in compari- In general rehabilitative efforts to preserve speech are unsatisfactory. A palatal lift has been with cinefluorography MND patients show ab- reported to be useful in patients who exhibit normalities in the first and second phases of velopharyngeal incompetence (Gonzalez and Ar- swallowing. In the first stage there is slowness of onson 1969). The use of silicone injection theore- the passage of the bolus from the mouth to the tically might benefit patients with weakness of pharynx and poor nasopharyngeal occlusion the vocal cords (Smith et al. 1967). As a general causing nasal regurgitation. In the second, liquid measure attention should be directed to lessening pools in the vallecula and pyriform recesses and secretions which can affect articulation. When can enter the laryngeal vestibule before elevation inability to talk is due to breathlessness patients of the larynx can protect the airway and prevent can regain the ability to speak after placement tracheal aspiration. Both bulbar and pseudobut- on a respirator. To achieve this, the tracheostomy bar disease can contribute to the problem. tube must be uncuffed when the patient wishes A few simple principles can help patients to speak or a specially adapted tube with an maintain their weight and minimize the risk of independent air supply must be employed (Smith aspiration. Liquids are usually harder to get and Norris 1975). down than solids. The taste and temperature of food can favorably influence swallowing. It is NUTRITION difficult for MND patients to eat with the head in an upright position. For a while attention to Most MND patients have inadequate caloric these details can help to offset a problem with intake even when no or mild dysphagia is mild dysphagia. More decisive action is dictated observed. This occurs when loss of appetite, by 3 factors: evidence for aspiration, dehydration, difficulty with food preparation or feeding pre- or severe weight loss. When indicated supplemen- cede problems with chewing and swallowing. By tal feeding is easily undertaken. Accordingly, this the time patients exhibit difficulty with semi-solid should not be delayed until there is a crisis. and pureed foods they may have experienced Further it is not, in our judgement, appropriate severe weight loss (20 25%). Surprisingly most to starve patients in the belief that this is a patients are at a loss to account for this, reporting merciful, final act. For terminal patients a simple that their diets are normal. nasogastric feeding tube is appropriate, Newer In normal fasting subjects, weight loss is versions are thin and flexible and thus well accompanied by a state of negative nitrogen tolerated for several weeks. Their drawbacks balance, indicating loss : of protein as well as fat include nasal and oropharyngeal irritation and (Davidson 1987). Since there is reason to assume for some a visible tube is offensive on aesthetic caloric restriction has the same effect on patients, grounds. The position of the tube needs to be it is likely that at least some of the muscle radiographically confirmed prior to institution of breakdown that occurs in MND is due to feeding to ensure correct placement in the small catabolism of muscle. Further there is evidence bowel. For long-term supplementation, percuta- of insulin resistance in MND which would be neous gastrostomy (PEG) is the procedure of expected to impair nutrition even with adequate choice (Larson et al. 1983). This ranks among caloric intake (Festoff 1987). Whatever the merits the major advances in symptomatic care to have of these factors, it is well established that been made available to MND patients. This malnourished MND patients who undergo a procedure, made possible as a result of technical feeding procedure stabilize or add to their weight. innovation, has enjoyed wide acceptance, displac- This would seem to argue for a dietary rather ing cervical esophagostomy and cricopharyngeal than metabolic cause for weight loss in MND. myotomy, which deserve mention only in histori- All phases of deglutition can be affected in cal context. The appeal of PEG is its ease of MND. Since the lower cranial nerves are dispro- implementation, minimal risk, and discomfort portionately involved, chewing and swallowing and avoidance of general anesthesia. Although it are invariably affected in the course of the disease can be performed in an outpatient setting, brief (Hillel and Miller 1989). On formal evaluation hospitalization (I 2 days) is preferred (Fig. 1). Ideally, the operation should be carried out as of protection of the pytorus a thinner tube can soon as indicated to minimize the risks due to be passed into the jejunum. Continuous feeding dehydration and other factors. The puncture site will then be required. is visualized either through an endoscope or in the radiology suite using fluoroscopy. Once the RESPIRATION site of placement has been identified a stab wound is made through the abdominal wall with The principal factors which can lead to respira- a large bore needle through which a guide wire tory complications in neuromuscular diseases are: and subsequently the tube is passed into the (1) aspiration; (2) diaphragmatic failure; (3) stomach. At the end of the procedure, air should impaired cough; (4) intercurrent respiratory infec- be removed from the stomach to prevent abdomi- tion; and (5) sleep apnea. nal distension which may compromise respiration. One of the main goals of regular follow up is Within 12 hours water can be introduced into to try to prevent potentially treatable problems the tube. Thereafter, feeding with a hospital such as aspiration from evolving into major, formula can begin initially at half strength and possibly fatal complications. Protection of the within 48 h at full strength. Feeding can be done airway may involve a feeding procedure in which by bolus, following the normal meal time pattern case a gastroenterologist may end up making a or by pump at a rate or I ml/min. This provides major contribution to the patient's pulmonary 1500-2000 calories per day. Complications in- well being. Decisions of this nature can safely be clude local and peritoneal infections, but serious made on clinical grounds, sometimes supple- problems are few and the wound site is usually mented with tests such as a swallowing study well healed and easily maintained with minimal which can demonstrate aspiration radiographi- daily care. If aspiration is a concern due to loss cally. To address the problem completely, atten- tion must also be directed to control of secretions which can be aspirated independently of food and liquids. In the effort to prevent pneumococcal pneumonia and influenza, vaccination may be employed, or in the case of the flu, amantadine may be prescribed prophylactically if there is a known exposure. Use of IPPB (intermittent positive pressure breathing) or an incentive spi- rometer may prevent atelectasis which can further embarrass pulmonary function (Fig. 2). The bene- fits of these and a myriad of other recommenda- tions of this sort have not specifically been tested in controlled studies. Diaphragmatic weakness is the principal cause for the inexorable deteriora- tion of pulmonary function that is seen over time in patients with MND (Howard et al. 1989). At rest the diaphragm contributes the major force of respiration (Derenne et al. 1978). Since innervation of the diaphragm originates from the midcervical spinal cord it is unduly susceptible because the disease preferentially involves the cervical segments early in the course of motor neuron disease (Wohlfart and Swank 1941). Unfortunately the thoracic and accessory muscles of respiration, which are relatively spafed due to their thoracic innervation, cannot easily compen- sate for diaphragmatic weakness. Two conse- quences result from this. There is progressive deterioration of pulmonary function, and clearing of secretions is made difficult due to the lack of a forceful cough. Respiratory complaints which should alert the physician to diaphragmatic failure include the presence of breathlessness at rest, particularly while supine, poor cough, and diminution in the volume of speech. Orthopnea occurs because the abdominal contents fall upon the diaphragm when patients are flat in bed. If the diaphragm is weak this adds a notable burden, resulting in dyspnea. This can be formally documented by a change in the vital capacity when the patient goes from the upright to a supine position (Howard et al. 1989) (Fig. 3). Pulmonary function studies can provide elo- quent documentation of the respiratory status of patients with neuromuscular disease, although there are pitfalls to their use especially in persons who have trouble holding a mouthpiece firmly in place (Griggs et al. 1980). In a hospital setting elaborate studies can be undertaken, but in the office small, relatively inexpensive electronic spi- rometers can be employed. Diaphragmatic weak- ness should be assessed by determining the maximal inspiratory pressure (MIP). Respiratory fatigue is best measured by maximum voluntary ventilation (MVV), and evidence for restriction of flow by measurement of the forced expiratory volume in I s (FEV-1) obtained during a forced vital capacity (FVC). Several detailed studies of pulmonary function have been undertaken in MND patients (Nakano et al. 1976; Fallat et al. 1979). Serial measure- ments in a group of patients demonstrated a gradual decline of FVC with more precipitous decline in the months before death. As a group MND patients show a decrease in total lung capacity and vital capacity and an increased residual volume. In some patients expiration may suddenly be interrupted, suggesting erratic closure of the glottis or vocal cords. This is best demonstrated in flow vs. volume studies (flow volume loops). Surprisingly patients with rather marked deterioration of ventilatory tests can maintain normal blood gases. Thus chronic patients may linger before succumbing to their hypoxemia and hypereapnia are not characteristic illness. For a time it is possible to provide of MND. respiratory assistance in the form of negative Sleep studies are probably underutilized in the pressure devices (cuirass, pneumobelt or tank), a case of MND. On several bases MND patients rocking bed, or by mask using intermittent ought to be unduly susceptible to disturbed sleep. positive pressure, but these options are temporary Under normal circumstances, collapse of the solutions (Bach et a]. 1987; Kerby et al. 1987). upper airway on inspiration is prevented in part Over the short term, assistive devices and possibly by muscular effort involving the tongue and medication may relieve muscular fatigue, which pharyngeal muscles. Weakness of these muscles has been thought to complicate respiratory failure along with accumulation of secretions should secondary to neuromuscular disease and carbon lead to obstruction of the airway resulting in dioxide retention (Shiffman and Belsh 1989). sleep apnea. Although expected, obstructive and Further, respiratory muscle fatigue can be ex- central sleep apnea have only recently been acerbated by intercurrent pulmonary infections described in MND (Carre et al. 1988, Howard et which should be treated vigorously unless a al. 1989). They are rarely seen as a presenting decision has been made to clefer further therapy. complaint. It is not certain that these problems To initiate long-term ventilatory support it is occur as often as would be anticipated, possibly necessary to proceed to tracheostomy and use of no more so than occurs in an older population. a positive pressure respirator. This can provide In patients who exhibit daytime somnolence or satisfactory ventilation for years. fatigue, treatment with continuous positive pres- A wise physician will anticipate the need for sure ventilation (CPAP) should be considered at life support prior to the occurrence of respiratory night with the goal of preventing hypoxemia and arrest. Considering the tremendous financial and hypercapnia, sleep fragmentation and daytime emotional demands, the decision making process symptoms (Howard et al. 1989). should involve thoughtful deliberation rather Although respiratory failure is usually insidious than rash action. To facilitate this, the wishes of in onset and evolution, it may occur suddenly, the patient and family about life support should sometimes as the initial presenting symptom be discussed at appropriate times during follow (Serpick et al. 1965). Respiratory distress is, of up and the patient should execute a directive to course, an ominous sign. In the majority of cases physicians. This insures compliance with the it signals a terminal stage of illness, but some patient's wishes under most circumstances. Al- though there are no absolute guidelines, in our function the patient learned to operate a personal opinion, life support should be reserved for computer using a microprocessor switch. A soft- patients who can be taken care of at home ware package allowed him to interface with the (Norris et al. 1987a). Ideally the patient should computer using Morse code. In 1985 a percutane- maintain use of an arm or hand, although this is ous gastrostomy was performed when it became only a relative consideration since over time most impossible for the patient to take food by mouth. patients become totally dependent. At the point This operation was complicated by cellulitis where the patient feels that prolongation of life which responded to antibiotic therapy. In 1987 is without purpose, it is ethical to disconnect the he developed cholecystitis. This was treated at respirator. Knowing that physicians are willing home with intravenous antibiotics. Hospital- to do this should be a comfort to persons who ization for aspiration pneumonitis was again elect to use a ventilator, but fear losing control required in the summer of 1989. Daily bronchos- over their destiny. The following case illustrates, copy and antibiotics were successfully employed from our point of view, a successful result. and the patient returned home. The patient, a 66-year-old male with MND, This case, which is not unique in our experience dating from 1977, presented with weakness of represents the successful management of a patient the left wrist followed by progressive weakness with advanced MND over a period of 10 years. of the limbs and neck musculature. As the disease Although this has entailed the expenditure of progressed noted shortness of breath was noted, enormous human and financial resources, hospi- especially when supine. In April of 1980 the talization has only been required on a few patient was hospitalized because of respiratory occasions and this has never been prolonged. failure. The following day a tracheostomy was Ignoring his considerable handicap, the patient performed and the patient was placed on a has managed a family business and maintained Bennett MA-1 respirator. Postoperatively his his role as head of his household. course was complicated by aspiration pneumonia. With resolution of this problem attention was SECRETIONS directed to returning the patient to his home. A portable, volume controlled respirator was ob- Drooling is one of the more vexing problems to tained. The cuffed tracheostomy tube was re- confront MND patients. In childhood salivary placed with a trachspeaking tube which allowed incontinence is acceptable, but for adults it is the patient to phonate without impeding ventila- humiliating. On clinical grounds drooling appears tory assistance. In the week before discharge the to be secondary to muscular weakness which patient was placed on a general medical ward compromises the containment or transport of where his family and care providers were compre- secretions (Smith and Goode 1970). Weakness of hensively trained in all aspects of his care. He the lower lip permits overflow from the mouth was discharged after 3 weeks of hospitalization, in some instances, but generally it is difficulty after which he was cared for at home. A number with swallowing that causes secretions to flood of modifications were made there to facilitate the oral cavity. Hypersalivation is unlikely to be bathing, transfer, and communication. A motor- the problem although this has not been carefully ized van with a hydraulic lift was obtained to studied. allow limited outings. Over the ensuing year Drooling is usually subtle at the outset, first speech was lost and in 1981 and 1982 he suffered noted on the pillow in the morning. Later it is bouts of pneumonia, secondary to aspiration. present while the patient is upright. Characteristi- Due to persistent tracheal irritation the standard cally, patients will be seen to frequently dab balloon cuffed tracheostomy tube which had been themselves with tissue. This can go almost used since the patient lost the ability to speak unnoticed or it can be extreme as a result of was replaced with a model employing a foam constant outpouring of saliva. Secretions may cuff. become extremely viscid, especially after con- In spite of almost complete loss of motor sumption of milk products. This may be partially relieved with the use of potassium iodide (SSKI), weakness, and rate of deterioration were similar n-acetylcysteine (mucomyst) or papase. Beyond in adjacent anatomic regions, implying that the matter of inconvenience and embarrassment MND exhibits a regional character. Over the associated with drooling, aspiration of saliva course of the illness deterioration was found to poses a constant risk in some patients. For both be generally linear, although at the outset and these reasons considerable attention has been end of the disease process patients could appear given to the management of this aspect of MND. to be stable. Carrying this type of analysis Approximately 1500ml of saliva is produced further, Brooks discerned that spread of the daily, the bulk of it by the major salivary glands disease is generally from closely approximated (Stuchell and Mandel 1988). Salivation is princi- anatomic sites (Brooks et al. 1990). Thus spread pally under the influence of the parasympathetic is typically from one limb to its fellow. nervous system. On this basis the mainstay of With the exception of temporary facilitation therapy is the use of medication with anticholiner- of strength with administration of edrophonium gic effects. This can be administered orally or via chloride in the instance of a pseudomyasthenic a skin patch. Amitriptyline hydrochloride, given syndrome which may occur in MND, there is nightly at the outset and then during the day little that can be currently done pharmacologi- once patients have accommodated to its sedative cally to alleviate weakness (Mulder et al. 1959). effect, is generally beneficial. A scopolamine It is commonly asked whether exercise is advis- patch, applied behind the ear for 24-72 h, reduces able. One can infer from studies with training salivary secretion more effectively than atropine programs that this is beneficial. In MND both (Talmi et al. 1988). Other drugs which may be maximum oxygen consumption and work capac- employed include trihexyphenidyl hydrochloride, ity drop in relation to loss of strength and the benzatropine mesylate, or propantheline bromide. normal metabolic responses to prolonged sub- It is important to recall that older patients maximal exercise are impaired (Karpati et al. medicated with anticholinergic drugs may develop 1979; Sanjak et al. 1987). With resistive training untoward complications including confusion, hal- endurance capacity has been shown to be con- lucinations, and urinary retention. siderably enhanced (McCartney et al. 1988). For instances of intractable drooling a number While medical professionals have historically of therapeutic strategies have been employed. been concerned about prescribing exercise for These attempt to alter the functional competence MND patients, due to the example of poliomyeli- of the salivary glands. Based on the fortuitous tis in which overwork weakness has been de- relation of the tympanic plexus and chorda scribed, it is reasonable to advise a program of tympani within the ear denervation of the salivary exercise for muscles which retain some strength glands can be accomplished readily with tympanic (Cashman et al. 1987; Milner-Brown and Miller neurectectomy (Goode and Smith 1970). Al- 1988). Although unproven, this may retard mus- though technically feasible, glandular excision, cular atrophy due to disuse, prevent contractures salivary duct ligation or diversion, or radiother- and minimize the risk of bedsores. When the apy are not advised. patient is unable to move a limb, passive exercise is indicated. In the presence of proximal upper WEAKNESS-SPASTICITY-CRAMPS extremity weakness, range of motion exercises are essential to prevent the patient from develop- Although muscular weakness is the hallmark of ing frozen shoulders. This is a common, extremely MND, it is only recently that the pattern of painful condition which can be prevented with weakness in MND has been characterized quanti- daily physical therapy. tatively. Munsat pioneered the longitudinal as- Spasticity, leading to contractures and scissor- sessment of maximum voluntary isometric ing of the lower extremities, is a management contraction as a means of documenting disease problem in some instances. Generally, it is not progression (Munsat et al. 1988). These studies prominent because lower motor neuron signs indicated that the time of onset, degree of predominate. Classically, spasticity was thought to result from hyperactive gamma discharge. organs which subsequently inhibit the motor More current is the notion that supraspinal neuron supplying the affected muscles (Botte et segments elicit presynaptic inhibition of fusimotor al. 1988). Prophylactic treatment traditionally fibers (la terminals) through release of GABA involves the administration of quinine sulfate or from inhibitory interneurons (Young and Weigh- phenytoin which are membrane stabilizing agents. ner 1987). In the case of a supraspinal lesion this These are usually administered at night. Based inhibition is lost leading to hypertonus. Further, on a recent report one might wonder whether spastic patients may be more handicapped by these medications are as effective as generally reduction in reciprocal inhibition than by hyper- thought (Warburton et al. 1987). excitability of the stretch reflex itself. The use of muscle relaxants in MND to deal ATYPICAL SYMPTOMS with spasticity may be of value, but can be disadvantageous (Landau 1974). Hypertonus of As a result of the predominance of motor the quadriceps and exaggeration of the extensor symptoms seen in MND, there are a variety of thrust reflex facilitate ambulation in paraparetic symptoms which are not considered to be 'classi- patients through a splinting effect. If medication cal' features of the disease. The prototypic patient is warranted, baclofen is probably the drug of is thought to be one whose mind, senses and choice. Prolonged administration of benzodiazep- sphincters are spared. Further, the disease is ines can be associated with depression. Dantrium generally pain-free except for the occurrence of sodium, which acts peripherally by reducing the cramps. Although this description usually holds, release of calcium from the sarcoplasmic reticu- physicians who see large numbers of patients are turn during muscle contraction, is contraindicated aware of the occurrence of atypical symptoms. (Rivera et al. 1975). In some patients it causes Patients may be demented, or have difficulties profound weakness. Temporary reduction of with language, and may exhibit extrapyramidal muscle tone may be obtained by cooling a limb signs. Alteration of taste and smell, common late with cold packs which reduces excitability of in the disease, may occur before the onset of muscle spindles and the input from cutaneous paralysis (Steele et al. 1990). While sensory pain receptors (Lenman 1985). In the rare in- complaints are minimal, sophisticated testing of stance of severe spasticity consideration can be altered sensation can be demonstrated (Dyck et given to the use of a motor point block to al. 1979). Severe pain, primarily involving the decrease spasticity of the hip adductors (Sinaki neck, back or limbs can bother patients at any 1988). time, even awakening them from sleep (Newrick Muscle cramps are an early, not generally and Langton-Hewer 1984). Loss of sphincter persistent, complaint. They characteristically control may occur as a result of impairment of occur with stretching at which time they involve autonomic regulation at the spinal or supra- the calf, hands, abdominal or chest muscles. nuclear level (Mitsumoto et al. 1988). Breakdown They are often preceded or accompanied by of skin is not common to MND, but patients fasciculations in the same muscle. Electromyogra- are not immune to this if they arc in bed or in a phy (EMG) has demonstrated that cramps are wheelchair much of the time. Protective cushions usually confined to part of a particular muscle and mattresses can minimize this problem. (Norris et al. 1957). They appear to be triggered When unusual symptoms occur, they obviously by hyperexcitability of the intramuscular portion should bring to mind the possibility of complicat- of motor nerve terminals, possibly as a result of ing factors and in some instances an alternative distortion of the nerve terminals upon muscle diagnosis. As more is written about motor neuron shortening or as a consequence of metabolic disease, the full extent of the syndrome will changes in the extracellular space which attend obviously be better understood. It is possible muscle contraction. The immediate remedy for that some of the unusual symptoms may be a cramps entails static stretching of the involved clue to the etiology of the disease, but this muscle. This may activate the Golgi tendon remains to be proven. Many of the non-specific symptoms of MND are amenable to treatment, decubitus ulcers responding to cleansing and application of an artificial covering, incontinence to the use of oxybutynin chloride or a catheter and pain to the administration of analgesics. ASSISTIVE DEVICES The primary purpose or rehabilitation procedures in MND is to maintain optimal functioning in the course of daily living, but the relationship between functional ability and equipment use is complex (Lord et al. 1987). Initially, all that may be necessary are simple orthotics such as a wrist splint or a foot lift. With progression of the disease, dependency on adaptive equipment increases. With loss of neck muscles, bracing is required to keep the head upright. The use of an underarm sling can minimize the effects of subluxation of the shoul- ders. For a time, specially designed utensils or dressing aids help the patient compensate for loss of hand function. While elaborate orthotic devices are sometimes prescribed, in practice these often prove to be cumbersome, expensive, and of limited utility (Newrick and Langton- Hewer 1984). As ambulation becomes more difficult, a cane or a walker is necessary, but at some point a wheelchair is indicated. This becomes mandatory when the patient begins to fall. Contemporary light weight chairs are easier to use and more portable. Self-propelled vehicles arc expensive, but if a patient is able to operate them, they ofter a degree of independence. With the addition of a portable respirator even patients with ad- vanced disease can be mobile using a van equipped with a hydraulic lift (Fig. 4). Modifications in the home are encouraged since it is the ideal setting for long-term care. Barriers to the free passage of a wheelchair need to be eliminated, entrances ramped and bath- rooms modified. Railings should be installed near the toilet and shower to provide support. A raised toilet seat and a chair in the shower can facilitate personal hygiene. A sliding board can be used to facilitate transfer from a wheelchair to a commode. If the patient is difficult to move, a hydraulic lift allows a lonc care provider to lower a patient in and out of a tub or from a bed to a wheelchair. An electric hospital type bed with overhead trapeze and an electric lift chair will fill out the furniture needs of most patients. A variety of mattresses are available which protect patients from developing decubitus ulcers. The greatest single advance for handicapped patients has been the availability of a range of consumer electronics, including telephones with automatic dialing, intercoms, alarms, printers, speech synthesizers, and computers. Linking some of these permits patients to control lights and appliances, and to communicate. Unfortunately, no currently available equipment imitates the intimacy of normal speech. Further, the interface between patient and machine is not ideal espe- cially for those who have limited use of their upper extremities. With even slight hand function, patients can input a computer using a micropro- cessor switch (Dymond et al. 1988). For com- pletely paralyzed patients, an infra-red switch triggered by eye blink can be employed. Two basic computer strategies are utilized. The patient can address the computer directly using Morse code or assemble information from a menu which is scrolled automatically before him on a monitor (Fig. 5). Irrespective of the system, communica- tion is painstakingly slow. This can be augmented by triggering phrases that are stored in a memory bank. If patients choose, they can vocalize their thoughts using a speech synthesizer. In spite of these advances, it is still common to see patients with sophisticated equipment using simple means such as an alphabet or ETRAN board to get their ideas across (Fig. 6). Based on the rapid advances of technology, it must be presumed that innovation will greatly enhance the lives of persons with neuromuscular disease in the years ahead. TERMINAL CARE Attitudes about death not only vary among individuals, but among cultures as well. Economic and other considerations may impinge on the decision to let a disease take its course, or to extend life as long as possible. A number of ethical and legal issues increasingly are being discussed for the purpose of establishing legal standards for care of the terminally ill (Beresford 1989). These have had the effect of protecting the patient's right to forgo treatment and the physician's right not to prolong life. The proper role for a physician in these matters is to serve the patient's interest rather than that of the state or some other party (Goldblatt 1984). In this capacity, physicians uphold the highest ideals of their profession and of society. In instances where the physician's values conflict with those of the patient, it is incumbent upon him to transfer responsibility to a colleague. There is now legal precedent in some countries for the withdrawal of life support systems (Wanzer et al. 1989). It is important for patients to inform their caretakers as to their wishes about such matters. This should be documented in the form of a 'living will'. Except in the Netherlands, euthanasia does not enjoy legal sanction (Singer and Siegler 1990). However, in the final stages of illness, the compassionate use of sedative medications is justified to relieve pain or suffering. This can be done in the hospital, or in the home in conjunction with hospices which generally distinguish themselves in the care of the terminally ill. CONCLUSION Physicians caring for persons with motor neuron disease can see parallels between themselves and those who cared for persons with poliomyelitis in the recent past. In both instances, there is no cure for the disease, Rather, symptomatic mea- sures are all that can be made available. Based on remarkable advances in technology, it is now possible to treat most of the symptoms of MND effectively. While theoretically the lives of patients can be extended for years, a number of human factors ultimately dictate whether the patient should embark on such a course. To resolve Mulder (Ed.), The Diagnosis and Treatment of these decisions requires considerable time and Amyotrophic Lateral Sclerosis. Boston, Houghton Mifflin Professional Publishers (1980) 322-325. insight, challenging physicians to realize the DARLEY, F. L., A. E. ARONSON and J. R. BROWN: Differential highest ideals of their profession. It can only be diagnostic patterns of dysarthria. J. Speech Hear- hoped that the intimate relationship between ing Res. 12 (t969) 246 269. patient and physician in these circumstances DAVIDSON,M.B.: Effect of growth hormone on carbo- hydrate and lipid metabolism. Endocr. Rev. 8 continues to be respected by the many parties (1987) 115 131. who are involved in the delivery of health care. DERENNE, J., P. T. MACKLEM and C. ROUSSOS: The respira- tory muscles: mechanics, control and pathophysi- ology. Am. Rev. Respir. Dis. 118 (1978) 373-390. Acknowlcdgements DYCK,P.J., J.C.STEVENS, D.W.MULDER and R.ESPINOSA: This chapter is dedicated to patients Charles Frequency of nerve fiber degeneration of periph- Bordner, Fred Clark, William Doro, Warren Irwin, eral motor and sensory neurons in amyotrophic Arthur Levien, Curtis Robert, John Stockton, and lateral sclerosis: morphometry of deep and super- James Waldal, and to friends and supporters: Cindy ficial peroneal nerves. Neurology 25 (1979) Beechner, Betty Bordner, Bruce Clark, William and 781 785. Ruth Frank, Arlene and George Hecht, Jack a@d DYMOND,E.A., R.POTTER, P.A.GRIFFITHs and E.J. Marianne Olson, Francis, Patty, Gloria and Wancia MCCLEMONT: A week in the life of Mary: the Stockton, and George and Joan Thagard. Colleagues impact of microtechnology on a severely handi- Benjamin Brooks, Forbes Norris, and Hiroshi M"- sumoto provided thoughtful comments, and Drs capped person. J. Biomed. Eng. 10 (1988) Robert Fallat and Gregory Weiner illustrations. 490. 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