The physician is initially put on the track of a myopathic disease by eliciting complaints of muscle weakness or fatigue, pain, limpness or stiffness, spasm, cramp, twitching, or a muscle mass or change in muscle volume. Of these, the symptom of weakness is by far the most frequent and at the same time the most elusive. As remarked in Chap. 24, when speaking of weakness, the patient often means excessive fatigability and poor endurance. Although fatigability in the strict sense of gradually reduced power with ongoing use of a muscle may be a feature of muscle diseases, particularly those affecting the neuromuscular junction such as myasthenia gravis, it is far more frequently a complaint of patients with chronic systemic disease or with anxiety or depression. As stated in Chap. 24, fatigue is an abstruse symptom, always requiring analysis and interpretation. When not attended by manifest reduction in muscle power, it is usually nonmuscular in origin. It may, on medical investigation, prove to be a systemic manifestation of infection, metabolic or endocrine disorder, severe anemia, reduced cardiopulmonary function, or neoplasia. More often, when expressed as a feeling of poor endurance, weariness, and disinclination to undertake or sustain mental and physical activity, it is indicative of neurasthenia, a psychiatric manifestation common to states of chronic anxiety and depression. An elusive syndrome of lifelong exercise intolerance, often accompanied by muscle cramps during exercise, has been traced in a limited number of cases to mutations in the cytochrome b gene of the mitochondrial DNA (Andreu et al), but these are rare. The subject of fatigue as a physiologic phenomenon and as a clinical feature of many psychiatric and medical diseases, including those that are predominantly myopathic, is considered fully in Chap. 24.
Evaluation of Muscle Weakness and Paralysis
Rather than relying on the patient's report to distinguish between fatigability and weakness, it is more informative to observe the patient during the performance of certain common activities such as walking, climbing stairs, and arising from a sitting, kneeling, squatting, or reclining position or using the arms over the head. Difficulty in performing these tasks signifies weakness rather than fatigue. Sometimes the weakness of a group of muscles becomes manifest only after a period of activity; for example, the feet and legs may "drag" only after the patient has walked a long distance. The physician, upon being told this by the patient, should attempt to conduct the examination under circumstances that duplicate the complaints. Of course, these impairments of muscle function may be caused by a neuropathic or central nervous system (CNS) disturbance rather than of a myopathic one, but usually these conditions can be separated by the basic methods indicated further on in this chapter and in Chaps. 3 and 24.
Reduced strength of muscle contraction—manifest by diminished power of single contractions against resistance (peak power) and during the sustained performance of prolonged or repetitive movements (i.e., endurance)—are the indubitable signs of muscle or neuromuscular disease. In such testing, the physician may encounter difficulty in enlisting the patient's cooperation. The tentative, hesitant performance of the asthenic or suggestible individual, or the hysteric or malingerer, poses difficulties that can be surmounted by experience and by the techniques described in Chap. 3. In infants and small children, who cannot follow commands, one assesses muscle power by the resistance to passive manipulation or by observing performance while the child is engaged in natural activities. The patient may be reluctant to fully contract the muscles in a painful limb; indeed, pain itself causes a reflex diminution in the power of contraction (algesic paresis). Estimating the strength of isometric contractions that do not require the painful part to be moved is a way around this difficulty.
Ascertaining the extent and severity of muscle weakness requires a systematic examination of the main groups of muscles. The patient is asked to contract each group with as much force as possible, while the examiner opposes the movement and offers a graded resistance in accordance with the degree of residual power (isokinetic contraction). Alternatively, the patient is asked to produce a maximal contraction and the examiner estimates power by the force needed to overcome or "break" it (isometric contraction or maximum voluntary isometric contraction). If the weakness is unilateral, one has the advantage of being able to compare it with the strength on the normal side. If it is bilateral, the physician must refer to his concept of what constitutes normalcy based on experience in muscle testing. With practice, one can distinguish true weakness from unwillingness to cooperate, feigned or neurasthenic weakness, and inhibition of movement by pain.
To quantitate the degree of weakness, a rating scale may be required. Widely used is the one proposed by the Medical Research Council (MRC) of Great Britain, which recognizes 6 grades of muscle strength as follows:
- 0—Complete paralysis
- 1—Minimal contraction
- 2—Active movement only with gravity eliminated
- 3—Full movement against gravity but cannot offer resistance to manual muscle opposition
- 4—Active movement against gravity and resistance but can be overcome by manual muscle opposition
- 5—Normal strength
Further gradations may be added, specified as 4+ for barely detectable weakness and 4 for easily detected weakness, 3+ and 3, and so on, allowing for 10 grades of power.
The ocular, facial, lingual, pharyngeal, laryngeal, cervical, shoulder, upper arm, lower arm and hand, truncal, pelvic, thigh, and lower leg and foot muscles are examined sequentially. In the case of muscle disease, it is most convenient to test the same muscle from each side. To fully and properly use tools such as the MRC scale and to detect mild weakness, muscles such as the neck flexors and extensors must be tested with the patient in the prone and supine positions. The anatomic significance of each of the actions tested, that is, what roots, nerves, and muscles are involved, can be determined by referring to Table 46-1. A practiced examiner can survey the strength of these muscle groups in 2 to 3 min.
A word of caution is in order: In manually resisting the patient's attempts to contract the large and powerful trunk and girdle muscles, the examiner may fail to detect slight degrees of weakness, particularly in well-muscled individuals. These muscle groups are best examined by having the patient use the muscle groups for their intended purposes: squat and kneel and then assume the erect posture, arise from and, walk on toes and heels, and lift a heavy object (e.g., Harrison's Principles of Internal Medicine) over his head. The strength of muscles of the hand can be quantified with a dynamometer; for research purposes, similar but more sophisticated devices exist for other muscle groups (see Fenichel et al). Nonetheless, the examiner should not dismiss the patient's complaint of weakness simply if it cannot be substantiated by the examination.
Changes in the Contractile Process and Definition of Terms
In the myasthenic states there is a rapid failure of contraction in the affected muscles during sustained or repetitive activity. For instance, after the patient looks upward at the ceiling for a few minutes, the eyelids progressively droop; closing the eyes and resting the levator palpebrae muscles causes the ptosis to lessen or disappear. Similarly, holding the eyes in a far lateral position will induce diplopia and strabismus. These effects, in combination with restoration of power by the administration of neostigmine or edrophonium, are the most valuable clinical criteria for the diagnosis of myasthenia gravis, as described in Chap. 49.
The opposite of the myasthenic phenomenon, an increment in power with a series of several voluntary contractions is a feature of the Lambert-Eaton myasthenic syndrome, which is associated in approximately 50 percent of cases with small cell carcinoma of the lung. The same increment occurs in botulism. In both instances there is an increase in the amplitude of compound muscle action potentials on the nerve conduction studies obtained following brief exercise (10 to 15 sec), or at high rates of repetitive nerve stimulation (20 to 50 Hz), as described in Chap. 45.
Other abnormalities may be discovered by observing the speed and efficiency of contraction and relaxation during one or a series of maximal actions of a group of muscles. In myxedema, for example, stiffness and slowness of contraction in a muscle such as the quadriceps may be seen on change in posture (contraction myoedema) and by direct percussion of a muscle, and there is an associated prolonged duration of the tendon reflexes. Slowness in relaxation of muscles is another feature of hypothyroidism, accounting for the complaint of uncomfortable tightness of proximal limb muscles. A curious rippling phenomenon in muscles may be the result of several processes and occurs as an inherited autosomal dominant trait. After a period of relaxation, stiffening and rippling occurs in the contracting or stretched muscles.
A prolonged failure of relaxation following contraction of a muscle is characteristic of myotonia, which typifies certain diseases: myotonia congenita, myotonic dystrophy, and paramyotonia congenita. True myotonia, with its prolonged discharge of membrane action potentials, requires strong contraction to elicit, is more evident after a period of relaxation, and tends to disappear with repeated contractions as discussed further in relation to the ion channel disorders in Chap. 50. This persistence of contraction is demonstrable also by tapping a muscle (percussion myotonia), a phenomenon easily distinguished from the electrically silent local bulge (myoedema) induced by tapping the muscle of a myxedematous or cachetic patient and from the brief fascicular contraction that is induced by tapping a normal or partially denervated muscle; the latter is referred to as idiomuscular contraction. In paramyotonia congenita one observes paradoxical myotonia, which refers to an increase in the degree of myotonia during a series of contractions (the reverse of what happens in the usual type of myotonia).
The effect of cold on muscle contraction may also prove informative; either paresis or myotonia, lasting for a few minutes, may be evoked or enhanced by cold. This is most prominent in the paramyotonia of Eulenburg, but it may occur to some degree in all the other myotonic disorders. Also, a cold pack applied to a ptotic eyelid of myasthenia will often reduce the weakness.
Myotonia and myoedema must also be distinguished from the recruitment and spread of involuntary spasm induced by strong and repeated contractions of limb muscles in patients with mild or localized tetanus, with the "stiff man" syndrome and with dystonias of various types. These are not primary muscle phenomena but are neural in origin, a result of an abolition of inhibitory mechanisms and also taken up in Chap. 50.
In practice, the term contracture is applied (somewhat indiscriminately as discussed previously) to all states of fixed muscle shortening. Several distinct types can be recognized. In true physiologic contracture a group of muscles, after a series of strong contractions, remain shortened for many minutes because of failure of the metabolic mechanism necessary for relaxation. In this shortened state, the electromyogram (EMG) remains relatively silent, in contrast to the high-voltage, rapid discharges observed with cramp, tetanus, and tetany. True physiologic contracture occurs in McArdle disease (phosphorylase deficiency), phosphofructokinase deficiency, and possibly in another condition, as yet undefined, where phosphorylase seems to be present. Yet another type of exercise-induced contracture, described originally by Brody, has been attributed by Karpati and coworkers to an autosomal recessive deficiency of calcium adenosine triphosphatase in the sarcoplasmic reticulum in type 2 muscle fibers. True contracture needs to be distinguished from paradoxical myotonia (see earlier) and from cramp, which in certain conditions (dehydration, tetany, pathologic cramp syndrome, amyotrophic lateral sclerosis [ALS]) can also be initiated by one or a series of strong voluntary muscle contractions.
It is appropriate here to comment on pseudocontracture (myostatic or fibrous contracture), for which the term contracture is used in general medicine. This is the common form of muscle and tendon shortening that follows prolonged fixation and inactivity of the normally innervated muscle (as occurs in a broken limb immobilized by a cast or flaccid weakness of a limb that is allowed to remain immobile). Here the shortened state of the muscle and tendons has no clearly established anatomic, physiologic, or chemical basis. Fibrosis of muscle, a state following chronic fiber loss and immobility of muscle, is another cause of muscle shortening. Depending on the predominant position, certain muscles are both weakened and shortened. Flexor fibrous contracture of the arms is a prominent feature of the Emery-Dreifuss form of muscular dystrophy. It also accounts for the rigidity and kyphoscoliosis of the spine, which are so frequently a part of myopathic diseases. The latter state is distinguished from ankylosis by the springy nature of the resistance, coincident with increased tautness of muscle and tendon during passive motion, and from Volkmann contracture, in which there is fibrosis of muscle and surrounding tissues as a result of ischemic injury, usually after a fracture of the elbow.
Arthrogryposis is another form of fibrous contracture that is found in newborns, involving multiple muscle groups; it occurs in association with several diseases that have two features in common: an onset during intrauterine life and an alteration of the neural or muscular apparatus that results in muscular weakness. In other words, contractures and fixity of the limbs in arthrogryposis are the result of reduced mobility of the developing joints, consequent upon muscle weakness during fetal development. Most often the cause is a loss or failure of development of anterior horn cells, as in Werdnig-Hoffman disease, but the abnormality may be in the nerve roots, peripheral nerves, or motor endplates, or in the muscle itself. The rigid spine syndrome (RSS) in children is yet another form of fibrous contracture, presumably the result of an unusual axial muscular dystrophy.
Notably, few of the primary muscle diseases are painful. When pain is prominent and continuous during rest and activity, there will usually be evidence of disease of the peripheral nerves, as in alcoholic–nutritional neuropathy, or of adjacent joints and ligaments (rheumatoid arthritis, polymyalgia rheumatica). Pain localized to a group of muscles is more a feature of torticollis and dystonias. Pain tends not to be prominent in polymyositis and dermatomyositis, but there are exceptions, as commented below. Pain tends to be more definite in polyneuritis, poliomyelitis, and polyarteritis nodosa than it is in polymyositis, various forms of dystrophy, and other myopathies. If pain is present in polymyositis, it usually indicates coincident involvement of connective tissues and joint structures. Hypothyroidism, hypophosphatemia, and hyperparathyroidism are other sources of a myalgic myopathy. Certain drugs produce muscle aches in susceptible individuals. They include the "statin" lipid-lowering drugs, clofibrate, captopril, lithium, colchicine, beta-adrenergic blocking drugs, penicillamine, cimetidine, suxamethonium, and numerous others (see the table contained in the review by Mastaglia and Laing).
There are probably a limited number of mechanisms of muscle pain. Prolonged and sustained contraction gives rise to a deep aching sensation. Contraction under ischemic conditions—as when the circulation is occluded by a tourniquet or from atherosclerotic vascular disease—induces pain; the pain of intermittent claudication is presumably of this type and is not accompanied by cramp. It was postulated that lactic acid or some other metabolite accumulates in muscles and activates pain receptors, but there is also evidence to the contrary. The delayed pain, swelling, and tenderness that occur after sustained exercise of unconditioned muscles are evidently a result of fiber necrosis (Armstrong).
Muscle biopsy infrequently reveals the cause of these painful syndromes, but it may be undertaken in cases of suspected metabolic or dystrophic muscle disease. In their retrospective series, Filosto and colleagues determined that the biopsy was most likely to be helpful if there was exercise-induced muscle pain and the creatine kinase (CK) concentration was greatly elevated; even then two-thirds of the entire group had either normal or nonspecific findings on the biopsy.
Having listed all these causes of proximal pains, all physicians are aware that arthritic and mundane musculoskeletal complaints are more common causes of discomfort.
Benign fasciculations, a common finding in otherwise normal individuals, can be identified by the lack of muscular weakness and atrophy and by the small-size muscle fascicles involved and repetitive appearance in only or regions. The recurrent twitches of the eyelid or muscles of the thumb experienced by most normal persons are often referred to inaccurately as "live flesh" or myokymia but are benign fasciculations of this type. Individuals with truly benign fasciculations have normal EMGs (i.e., they have no fibrillations) as demonstrated in a large series of such patients studied and followed for many years by Blexrud and colleagues. Myokymia is a less common condition, in which there are repeated twitchings and rippling of a muscle at rest.
Muscle cramps, despite their common occurrence, are a poorly understood phenomenon. They occur at rest or with movement (action cramps), and they are frequently reported in motor system disease, tetany, dehydration after excessive sweating and salt loss, metabolic disorders (uremia and hemodialysis, hypocalcemia, hypothyroidism, and hypomagnesemia), and certain muscle diseases (e.g., rare cases of Becker muscular dystrophy and congenital myopathies). Gospe and colleagues reported a familial (X-linked recessive) type of myalgia and cramps associated with a deletion of the first third of the dystrophin gene, which is the one implicated in Duchenne dystrophy; strangely, there was no weakness or evidence of dystrophy. Lifelong, severe cramping of undetermined type has also been seen in a few families. The dramatic Satoyoshi syndrome is characterized by continuous, painful leg cramps, alopecia universalis, and diarrhea.
Far more frequent than all these types of cramping, and experienced at one time or another by most normal persons, is the benign form (idiopathic cramp syndrome) in which no other neuromuscular disturbance can be found. Most often benign cramps occur at night and affect the muscles of the calf and foot, but they may occur at any time and involve any muscle group. Some patients state that cramps are more frequent when the legs are cold and daytime activity has been excessive. In others, the cramps are provoked by the abrupt stretching of muscles, are very painful, and tend to wax and wane before they disappear. The EMG counterpart is a high-frequency discharge. Although of no pathologic significance, the cramps in extreme cases are so persistent and readily provoked by innocuous movements as to be disabling. Cramps of all types need to be distinguished from sensations of cramp without muscle spasm. The latter is a dysesthetic phenomenon in certain polyneuropathies. The disorders that simulate cramps, such as stiff-man syndrome and other forms of continuous muscle fiber activity that have various bases, is discussed in Chap. 50.
Contrasted to cramp is the already described physiologic contracture, observed in McArdle disease and related metabolic myopathies, in which increasing muscle shortening and pain gradually develop during muscular activity. Unlike cramping, it does not occur at rest, the pain is less intense, and the EMG of the contracted muscle at the time is relatively silent. Continuous spasm intensified by the action of muscles and with no demonstrable disorder at a neuromuscular level is a common manifestation of localized tetanus and also follows the bite of the black widow spider. There may also be difficulty distinguishing cramps and spasms from the early stages of a dystonic illness.
Altered structure and function of muscle are not accurately revealed by palpation. Of course, the difference between the firm, hypertrophied muscle of a well-conditioned athlete and the slack muscle of a sedentary person is as apparent to the palpating fingers as to the eye, as is also the persistent contraction in tetanus, cramp, contracture, fibrosis, and extrapyramidal rigidity. The muscles in dystrophy are said to have a "doughy" or "elastic" feel, but we find this difficult to judge. In the Pompe type of glycogen storage disease, attention may be attracted to the musculature by an unnatural firmness and increase in bulk. The swollen, edematous, weak muscles in acute rhabdomyolysis with myoglobinuria or severe polymyositis may feel taut and firm but are usually not tender. Areas of tenderness in muscles that otherwise function normally, a state called myogelosis, have been attributed to fibrositis or fibromyositis, but their nature has not been divulged by biopsy.
Topography and Patterns of Myopathic Weakness
In almost all the diseases under consideration, some muscles are affected and others spared, each disease displaying its own pattern. Restated, the topography or distribution of weakness tends to be alike in all patients with the same disease. The pattern of weakness is as important a diagnostic attribute of muscular disease as for the various diseases of the peripheral nervous system discussed in Chap. 46, but the configurations differ in important ways. As a general rule, muscle diseases are identified by a predominantly proximal weakness that is symmetric.
The following patterns of muscle involvement constitute a core of essential clinical knowledge in this field. Subacute and chronic evolution of weakness is distinguished in each category from more acute causes.
Ocular Palsies Presenting as Ptosis, Diplopia, and Strabismus
Primary diseases of muscle do not involve the pupil, and in most instances their effects are bilateral. In lesions of the third, fourth, or sixth cranial nerves, a neural origin is disclosed by the pattern of ocular muscle palsies, abnormalities of the pupil, or both. When weakness of the orbicularis oculi (muscles of eye closure) is added to weakness of eye opening (levator palpebrae; ptosis), it nearly always signifies myasthenia gravis and occasionally, a rare primary disease of muscle (progressive external ophthalmoplegia [PEO]). Other causes of subacute and chronic development of relatively pure weakness of the muscles of eye movement are oculopharyngeal dystrophy, and exophthalmic (hyperthyroid) ophthalmopathy. In PEO, the muscles, including the levators of the eyelids, become paralyzed almost symmetrically over a period of years. In most cases, this disorder is a form of mitochondrial myopathy. Oculopharyngeal dystrophy involves primarily the levators of the eyelids and, to a lesser extent, other eye muscles and pharyngeal-upper esophageal striated muscles. It begins in middle or late adult life and later, and—like PEO—tends only decades later to involve girdle and proximal limb muscles.
There are several other less common chronic myopathies in which external ophthalmoplegia is associated with involvement of other muscles or organs, namely, the congenital ophthalmoplegia of the Goldenhar-Gorlin syndrome (see Aleksic et al); the Kearns-Sayre syndrome (retinitis pigmentosa, heart block, short stature, generalized weakness, and ovarian hypoplasia); other congenital myotubular and mitochondrial myopathies; and nuclear ophthalmoplegia with bifacial weakness (Möbius syndrome). Rarely, eye muscle weakness may occur at a late stage in a few other dystrophies and ptosis has a wider diagnostic range that includes myotonic dystrophy. Although not a regular feature of the disease, ophthalmoparesis can occur in the Lambert-Eaton myasthenic syndrome.
Ptosis is variable in all of these conditions. When present in infantile myopathic disease, it is frequently a marker of the congenital myasthenic syndromes. Trichinosis is a rare cause, associated also with periorbital edema.
Bifacial Palsy Presenting as an Inability to Smile, to Expose the Teeth, and to Close the Eyes
Varying degrees of bifacial weakness are observed in myasthenia gravis, usually conjoined with ptosis and ocular palsies. On occasion, weakness of facial muscles may be combined with myasthenic weakness of the masseters and other bulbar muscles without involvement of ocular muscles. Facial weakness and ptosis are features of myotonic dystrophy. More severe or complete facial palsy occurs in facioscapulohumeral dystrophy, sometimes presenting several years before weakness of the shoulder girdle muscles. Bifacial weakness is also a feature of certain congenital myopathies (centronuclear, nemaline), Kennedy type of degenerative bulbospinal motor neuron disease, and the Möbius syndrome of the absence of the facial nuclei (in combination with abducens palsies).
Advanced scleroderma, Parkinson disease, or a pseudobulbar state can immobilize the face to the point of simulating myopathic or neuropathic paralysis, but always in a context that makes the cause obvious.
Bulbar (Oropharyngeal) Palsy Presenting as Dysphonia, Dysarthria, and Dysphagia With or Without Weakness of Jaw or Facial Muscles
Myasthenia gravis is the most frequent cause of this syndrome and must also be considered whenever a patient presents with the solitary finding of a hanging jaw or fatigue of the jaw while eating or talking; usually, however, ptosis and ocular palsies are conjoined. Dysphagia and dysphonia may be early and prominent signs of polymyositis, as well as inclusion body myositis (IBM), and may appear in patients with myotonic dystrophy, because of upper esophageal atonia.
Combinations of these palsies are not typically of muscular or neuromuscular origin but instead are observed as an acute syndrome in botulism, in brainstem stroke, and at the outset of Guillain-Barré syndrome. Diphtheria and bulbar poliomyelitis are now rare diseases that may present in this way. Progressive bulbar palsy (motor neuron disease) may be the basis of this syndrome (see Chap. 39); the last of these diagnoses is most obvious when the tongue is withered and twitching. Syringobulbia, basilar invagination of the skull, and certain types of Chiari malformation may reproduce some of the findings of bulbar palsy by involving the lower cranial nerves. Rare cases of progressive aphonia include the X-linked Kennedy syndrome of bulbospinal atrophy.
Cervical Palsy Presenting With Inability to Hold the Head Erect or to Lift the Head from the Pillow ("Hanging, or Dropped, Head" Syndrome, "Camptocormia")
This is caused by weakness of the posterior neck muscles and of the sternocleidomastoids and other anterior neck muscles. In advanced forms of this syndrome, the head may hang with chin on chest unless the patient holds it up with the hands. There may be difficulty differentiating the condition from a dystonic anterocollis; in the latter there is palpable tonic spasm of the sternomastoid and posterior neck muscles. A pattern of neck and spine extensor weakness also occurs in advanced Parkinson disease. A common error in all these cases is to attribute the problem to structural disease of the cervical spine.
This topographic pattern occurs most often in idiopathic polymyositis and IBM, in which cases it is often combined with mild dysphagia, dysphonia, and weakness of girdle muscles. The same symptom may be a feature of motor neuron disease and is infrequently the presenting feature of that process. Myasthenic patients commonly complain of an inability to hold up their heads late in the day; both flexors and extensors of the neck are found to be weak. Occasionally, this pattern of weakness is observed in patients with nemaline rod myopathy. Cases of hanging head have appeared many years after local radiation of the neck and thorax for Hodgkin disease as described by Rowin and colleagues and with syringomyelia (Nalini and Ravishankar).
There is, in addition, a poorly characterized local myopathic process isolated to the cervical paraspinal muscles, which has no distinguishing histopathologic or histochemical features but has accounted for many of the cases of neck extensor weakness that we have encountered. The condition is observed in elderly persons, in some series mainly men, but our experience has included as many women. There is severe but relatively nonprogressive weakness of the neck extensors and only mild weakness of shoulder girdle and proximal arm muscles. Katz and colleagues have suggested the designation "isolated neck extensor myopathy" in preference to dropped head syndrome. What has been referred to as a bent spinesyndrome (for which the term camptocormia is also used) is probably the same entity and may follow after years of the condition affecting the neck, or it may surface independently. These conditions of cervical weakness are reviewed by Umapathi and colleagues and by Azher and Jankovic. Several recent series have suggested that mutations in RYR1 that encodes for ryanodine receptor may be a common cause of late onset axial myopathy and neck extensor weakness-bent spine syndrome (Løseth et al). Mutations in RYR1 are more commonly associated with the central core congenital myopathy or malignant hyperthermia as noted in a later section.
The major types of progressive muscular dystrophies, when advanced, usually affect the anterior neck muscles severely. Syringomyelia, spinal accessory neuropathy, some form of meningoradiculitis, and loss of anterior horn cells in conjunction with systemic lymphoma or carcinoma may differentially paralyze the various neck muscles.
Weakness of Respiratory and Trunk Muscles
Usually the diaphragm, chest, and trunk muscles are affected in association with shoulder and proximal limb muscles, but occasionally, isolated weakness of the respiratory muscles is the initial or the dominant manifestation of a muscle disease. Dyspnea and diminished vital capacity first bring the patient to the pulmonary clinic. The main causes are motor neuron disease, myasthenia gravis and less often because of their rarity, glycogen storage disease (acid maltase deficiency—Pompe disease), mitochondrial myopathies, and nemaline myopathy. Polymyositis may cause respiratory weakness, but pulmonary difficulty is more often the result of interstitial lung disease. Unilateral paralysis of the diaphragm may result from compression of the phrenic nerve in the thorax by tumor or aortic aneurysm; an idiopathic or postinfectious variety may be related to brachial plexitis (see Chap. 46). The diaphragm and accessory muscles may be severely affected in some types of muscular dystrophies, but usually in association with pelvocrural and shoulder muscle weakness. Nocturnal dyspnea, sleep apnea, and respiratory arrest may occur, particularly in myasthenics and in patients with glycogen storage myopathies, and respiratory failure may threaten life in severe myasthenia gravis, Guillain-Barré syndrome, and poliomyelitis.
As a general observation, in the acute neuromuscular paralyses, the cervical and shoulder muscles and the diaphragm, all of which share a common innervation, show a similar degree of weakness. Asking the patient to count aloud on 1 maximal breath can help detect diaphragmatic weakness (counting to 20 equates with a vital capacity of approximately 2 L). Paradoxical inward movement of the abdomen with inspiration is another sign of diaphragm weakness. Disorders of breathing and ventilation are discussed in Chaps. 26 and 46 in relation to its most dramatic presentation in the Guillain-Barré syndrome.
Bibrachial Palsy and the Dangling-Arm (Flail-Arm) Syndrome
Weakness, atrophy, and fasciculations of the hands, arms, and shoulders characterize the common form of motor neuron disease, ALS. Primary diseases of muscle hardly ever weaken these parts disproportionately. A diffuse weakness of both arms and the shoulder muscles may occur in the early stages of Guillain-Barré syndrome, paraneoplastic neuropathy, and amyloid polyneuropathy, in special forms of immunoglobulin (Ig) M-related paraproteinemic, or in inflammatory polyneuropathy (e.g., brachial neuritis) and porphyric polyneuropathy. A lesion affecting the central portion of the spinal cord in the cervical region produces this same pattern, but in that case there is an associated loss of pain and thermal sensation in the upper limbs and shoulders, signs that exclude disease of muscle.
Proximal Limb-Girdle Palsies Presenting as Inability to Raise the Arms or to Arise From a Squatting, Kneeling, or Sitting Position
This is the common pattern of a number of myopathies. Polymyositis, IBM, dermatomyositis, and the muscular dystrophies most often manifest themselves in this fashion. The endocrine and the acquired metabolic myopathies (e.g., Cushing disease, hyperthyroidism, and steroid or statin administration) are other typical causes. Proximal limb weakness is a feature of myasthenia but almost always after the development of ocular or pharyngeal involvement. The childhood Duchenne, Becker, and limb-girdle types of dystrophies tend first to affect the muscles of the pelvic girdle, gluteal region, and thighs, resulting in a lumbar lordosis and protuberant abdomen, a waddling gait, and difficulty in arising from the floor and climbing stairs without the assistance of the arms. Climbing up by placing the hands on the thighs (Gower sign) is particularly characteristic of the dystrophies. Facioscapulohumeral dystrophy affects the muscles of the face and shoulder girdles foremost, and it is manifest by incomplete eye closure, inability to whistle and to raise the arms above the head, winging of the scapulae, and thinness of the upper arms with preserved forearm bulk ("Popeye" effect). Certain early or mild forms of dystrophy may selectively involve only the peroneal and scapular muscles. In milder forms of polymyositis, weakness may be limited to the neck muscles or to the shoulder or pelvic girdles.
A number of other diseases of muscle may express themselves by a disproportionate weakness of girdle and proximal limb musculature. An intrinsic metabolic myopathy, such as the adult form of acid maltase deficiency and the familial types of periodic paralysis, may affect only this region. The congenital myopathies (central core, nemaline, myotubular) cause a relatively nonprogressive weakness of girdle muscles more than distal ones. Proximal muscles are occasionally implicated in spinal muscular atrophy or late onset type and in Kennedy bulbospinal atrophy.
Bicrural Palsy Presenting as Lower Leg Weakness With Inability to Walk on the Heels and Toes, or as Paralysis of All Leg Muscles
With the exception of certain distinctive distal types of muscular dystrophies, this pattern, usually due to weakness of peroneal, anterior tibial, and thigh muscles, is usually not a result of myopathy. Symmetrical weakness of the lower legs is more often caused by polyneuropathy. In cases of total leg and thigh weakness, one first considers a spinal cord disease. Motor neuron disease may begin in the legs, asymmetrically and distally as a rule, and affect them disproportionately to other parts of the body. Thus the differential diagnosis of distal or generalized leg weakness involves more diseases than are involved in the restricted paralyses of other parts of the body.
Isolated Quadriceps Femoris Weakness
Isolated quadriceps femoris weakness may be the expression of several diseases. In adults, the most common cause is IBM (where it may be unilateral or asymmetrical) or, a restricted form of Becker muscular dystrophy. In thyrotoxic and steroid myopathies, the major effects are on the quadriceps muscles. If unilateral or bilateral with loss of patellar reflex and sensation over the inner leg, this condition is most often the result of a femoral neuropathy, as occurs from diabetes, or of an upper lumbosacral plexus lesion. Injuries to the hip and knee cause rapid disuse atrophy of the quadriceps muscles. A painful condition of infarction of the muscle on 1 side is seen in diabetic patients.
Distal Bilateral Limb Palsies Presenting as Foot-Drop with Steppage Gait (With or Without Pes Cavus), Weakness of All Lower Leg Muscles, and Later Wrist-Drop and Weakness of Hands
The principal cause of this syndrome is a familial polyneuropathy, mainly of the Charcot-Marie-Tooth type (see Chap. 46); the course is over decades. Chronic nonfamilial polyneuropathies, particularly paraproteinemic and inflammatory ones with motor conduction block and exceptionally, some forms of familial progressive muscular atrophy and distal types of progressive muscular dystrophy, and sarcoid myopathy may also present in this way. In myotonic dystrophy, there may be weakness of the leg muscles as well as the forearms, sternocleidomastoids, face, and eyes. With these exceptions, the generalization that girdle weakness without sensory changes is indicative of myopathy and that distal weakness is indicative of neuropathy is clinically useful.
Generalized or Universal Paralysis: Limb (but Usually Not Cranial) Muscles, Involved Either in Attacks or as a Chronic Persistent, Progressive Deterioration
When acute in onset and episodic, this syndrome is usually a manifestation of familial or acquired hypokalemic or hyperkalemic periodic paralysis. One variety of the hypokalemic type is associated with hyperthyroidism, another with hyperaldosteronism. Attacks of porphyric neuropathy and of Refsum disease with generalized weakness have an episodic nature. Widespread paresis (rather than paralysis) that has an acute onset and lasts many weeks is at times a feature of a severe form of idiopathic or parasitic (trichinosis) polymyositis and, rarely, of the toxic effects of certain pharmaceutical agents, particularly those used to treat hypercholesterolemia. Idiopathic polymyositis and, rarely, IBM may involve all limb and trunk muscles, but usually spare the facial and ocular muscles, whereas the weakness in trichinosis is mainly in the ocular and lingual muscles. In infants and young children, a chronic and persistent generalized weakness of all muscles, except those of the eyes, always raises the question of Werdnig-Hoffman spinal muscular atrophy or, if milder in degree and relatively nonprogressive, of one of the congenital myopathies or polyneuropathies. In these diseases of infancy, paucity of movement, hypotonia, and retardation of motor development may be more obvious than weakness, and there is arthrogryposis at birth.
Paralysis of Single Muscles or a Group of Muscles
This is usually neuropathic, less often spinal or myopathic. Muscle disease does not need to be considered except in certain instances of pressure-ischemic necrosis of muscle as a result of local pressure or infarction, as in monoplegic alcoholic myopathy or in diabetic muscle infarction. The weakness of IBM has a preference for certain sites, specifically parts of the quadriceps, or of the forearm muscles, particularly the long finger flexors (flexor digitorum profundus), and also therefore enters into consideration.
From this exposition of the topographic aspects of weakness, one can appreciate that each neuromuscular disease exhibits a predilection for particular groups of muscles. Apart from these patterns that suggest certain possibilities of disease and exclude others, diagnosis depends on the age of the patient at the time of onset and tempo of progression, the coexistence of medical disorders, certain laboratory findings (serum concentrations of muscle enzymes, EMG, and biopsy findings), and genetic determinants.
The symptoms and signs of muscle disease are considered in this chapter mainly in connection with the age of the patient at the time of onset, their mode of evolution, and the presence or absence of familial occurrence. Because many muscle diseases are hereditary, a careful family history is important. The pattern of inheritance has diagnostic significance and, if genetic counseling or prenatal diagnosis is a consideration, a detailed genealogic tree becomes essential. When historical data are insufficient, it is often necessary to examine siblings and parents of the proband. The molecular genetics and other genetic aspects of the heritable muscle diseases, subjects of intense interest in recent years, are discussed at appropriate points in the chapter.
In summary, the clinical recognition of myopathic diseases is facilitated by a prior knowledge of a few topographic syndromes, the age of the patient at the onset of the illness, a familial occurrence of the same or similar illnesses, and of the medical setting in which weakness evolves. Diagnostic accuracy is aided by the intelligent use of the laboratory examinations discussed in Chap. 45, particularly the muscle enzymes, EMG, and muscle biopsy.