Neurology_Adams

Neurology_Adams. Involuntary recurrent spasm of both eyelids (blepharospasm, as discussed in Chaps. 4 and 13) may occur with almost any form of dystonia, but is most frequent in elderly persons as an isolated phenomenon, and there may be varying degrees of spasm of the other facial muscles. Although relaxant and tranquilizing drugs are of little help in this disorder, injections of botulinum toxin into the orbicularis oculi muscles can reduce the excessive blinking. A few of our patients have been helped (paradoxically) by l-dopa; baclofen, clonazepam, and tetrabenazine in increasing doses may be helpful as well. In the past, failing these measures, the periorbital muscles were destroyed by injections of doxorubicin or surgical myectomy. With the advent of botulinum treatment, there is no longer a need to resort to these extreme and irreversible measures. In some cases, blepharospasm subsides spontaneously. Rhythmic unilateral myoclonus, akin to palatal myoclonus (actually a tremor as noted in Chap.


Neurology_Adams

Neurology_Adams. resort to these extreme and irreversible measures. In some cases, blepharospasm subsides spontaneously. Rhythmic unilateral myoclonus, akin to palatal myoclonus (actually a tremor as noted in Chap. 4), may be restricted to facial, lingual, or laryngeal muscles.


Neurology_Adams

Neurology_Adams. Hypersensitivity of the facial nerve occurs in hypocalcemic tetany; spasm of the facial muscles is elicited by tapping in front of the ear (Chvostek sign) but this phenomenon is also seen in many normal individuals. The Ninth, or Glossopharyngeal, Nerve


Neurology_Adams

Neurology_Adams. This nerve arises from the lateral surface of the medulla by a series of small roots that lie just rostral to those of the vagus nerve. The glossopharyngeal, vagus, and spinal accessory nerves leave the skull together through the jugular foramen and are then distributed peripherally. The ninth nerve is mainly sensory, with cell bodies in the inferior, or petrosal, ganglion (the central processes of which end in the nucleus solitarius) and the small superior ganglion (the central fibers of which enter the spinal trigeminal tract and nucleus). Within the nerve are afferent fibers from baroreceptors in the wall of the carotid sinus and from chemoreceptors in the carotid body. The baroreceptors are involved in the regulation of blood pressure, and chemoreceptors are responsible for the ventilatory responses to hypoxia. The somatic efferent fibers of the ninth nerve are derived from the nucleus ambiguus, and the visceral efferent (secretory) fibers, from the inferior salivatory nucleus.


Neurology_Adams

Neurology_Adams. responses to hypoxia. The somatic efferent fibers of the ninth nerve are derived from the nucleus ambiguus, and the visceral efferent (secretory) fibers, from the inferior salivatory nucleus. These fibers contribute in a limited way to the motor innervation of the striated musculature of the pharynx (mainly of the stylopharyngeus, which elevates the pharynx), the parotid gland, and the glands in the pharyngeal mucosa. A discussion of its role in swallowing is found in Chap. 25.


Neurology_Adams

Neurology_Adams. It is commonly stated that the glossopharyngeal nerve mediates sensory impulses from the faucial tonsils, posterior wall of the pharynx, and part of the soft palate as well as taste sensation from the posterior third of the tongue. However, an isolated lesion of the ninth cranial nerve is a rarity and therefore the effects are not fully known. In one personally observed case of bilateral surgical interruption of the ninth nerves, verified at autopsy, there had been no demonstrable loss of taste or other sensory or motor impairment. This suggests that the tenth nerve may be responsible for these functions, at least in some individuals. The role of the ninth nerve in the reflex control of blood pressure and ventilation has been alluded to earlier but referable clinical manifestations from damage of this cranial nerve are infrequent except perhaps for syncope as noted below.


Neurology_Adams

Neurology_Adams. One may occasionally observe glossopharyngeal palsy in conjunction with vagus and accessory nerve involvement because of a tumor in the posterior fossa or an aneurysm or intracranial dissection of the vertebral artery, or thrombosis of the sigmoid sinus or internal jugular vein. The nerves may be compressed as they pass through the jugular foramen. Hoarseness as a result of vocal cord paralysis, some difficulty in swallowing, deviation of the soft palate to the sound side, anesthesia of the posterior wall of the pharynx, and weakness of the upper trapezius and sternomastoid muscles make up the clinical picture (see Table 44-1, jugular foramen syndrome). On leaving the skull, the ninth, tenth, and eleventh nerves lie adjacent to the cervical internal carotid artery, where they can be damaged (presumably made ischemic) by a dissection of that vessel. Glossopharyngeal Neuralgia (Also Discussed in Chap. 9)


Neurology_Adams

Neurology_Adams. Glossopharyngeal Neuralgia (Also Discussed in Chap. 9) This disorder, first described by Weisenburg in 1910, resembles trigeminal neuralgia in many respects except that the unilateral stabbing pain is localized to one side of the root of the tongue and throat. It is far less common than trigeminal neuralgia. Sometimes the pain overlaps the vagal territory beneath the angle of the jaw and external auditory meatus. It may be triggered by coughing, sneezing, swallowing, and pressure on the tragus of the ear. Temporary blocking of the pain by anesthetizing the tonsillar fauces and posterior pharynx with 10 percent lidocaine spray is diagnostic. Rarely, herpes zoster may involve the glossopharyngeal nerve. Fainting as a manifestation of vagoglossopharyngeal neuralgia is described in Chap. 9.


Neurology_Adams

Neurology_Adams. The same antiepileptic and other drugs that are helpful in the treatment of tic douloureux may be used to treat glossopharyngeal neuralgia, but their efficacy is difficult to judge. Regarding vascular compression of the nerve as a cause of glossopharyngeal neuralgia, Resnick and colleagues have reported the results of microvascular decompression of the ninth nerve in 40 patients; in 32 of these, relief of symptoms was complete and was sustained during an average followup of 4 years; 3 patients remained with permanent weakness of structures ostensibly innervated by the ninth nerve. A similar high rate of success has been achieved by others. If syncope is associated with the pain, it can be expected to cease with abolition of the attacks of pain. Syncope can also occur when the ninth nerve is involved by tumors of the parapharyngeal space; most of these are squamous cell carcinomas and both the ninth and tenth nerves are implicated. Section of rootlets of the ninth nerve has reportedly


Neurology_Adams

Neurology_Adams. is involved by tumors of the parapharyngeal space; most of these are squamous cell carcinomas and both the ninth and tenth nerves are implicated. Section of rootlets of the ninth nerve has reportedly reduced or abolished the episodes of fainting in these cases.


Neurology_Adams

The Tenth, or Vagus, Nerve

Neurology_Adams. The Tenth, or Vagus, Nerve


Neurology_Adams

Neurology_Adams. This nerve has an extensive sensory and motor distribution and important autonomic functions. It has two ganglia: the jugular, which contains the cell bodies of the somatic sensory nerves (innervating the skin in the concha of the ear), and the nodose, which contains the cell bodies of the afferent fibers from the pharynx, larynx, trachea, esophagus, and thoracic and abdominal viscera. The central processes of these two ganglia terminate in the nucleus of the spinal trigeminal tract and the tractus solitarius, respectively. The motor fibers of the vagus are derived from 2 nuclei in the medulla—the nucleus ambiguus and the dorsal motor nucleus. The former supplies somatic motor fibers to the striated muscles of the larynx, pharynx, and palate; the latter supplies visceral motor fibers to the heart and other thoracic and abdominal organs. The distribution of vagal fibers is illustrated in Fig. 44-4, and their participation in swallowing is described in Chap. 25.


Neurology_Adams

Neurology_Adams. Complete interruption of the intracranial portion of one vagus nerve results in a characteristic pattern of paralysis. The soft palate droops on the ipsilateral side and does not rise in phonation. The uvula often, but not always, deviates to the normal side on phonation. There is loss of the gag reflex on the affected side and of the curtain movement of the lateral wall of the pharynx, whereby the faucial pillars move medially as the palate rises in saying “ah.” The voice is hoarse, often nasal, and the vocal cord on the affected side lies immobile in a “cadaveric” position, that is, midway between abduction and adduction. With partial lesions, movements of abduction are affected more than those of adduction (Semon’s law). There may be a loss of sensation at the external auditory meatus and back of the pinna. Usually no change in visceral function can be demonstrated with a unilateral lesion except by special autonomic testing. If the pharyngeal branches of both vagi are affected, as


Neurology_Adams

Neurology_Adams. back of the pinna. Usually no change in visceral function can be demonstrated with a unilateral lesion except by special autonomic testing. If the pharyngeal branches of both vagi are affected, as in diphtheria, the voice has a nasal quality, and regurgitation of liquids through the nose occurs during the act of swallowing.


Neurology_Adams

Diseases Affecting the Vagus

Neurology_Adams. Diseases Affecting the Vagus


Neurology_Adams

Neurology_Adams. Complete bilateral paralysis is said to be incompatible with life, and this is probably true if the nuclei are entirely destroyed in the medulla by poliomyelitis or some other disease. However, in the cervical region, both vagi were blocked with procaine in the treatment of intractable asthma in past days without mishap. Of interest in this regard, Johnson and Stern reported a case of bilateral vocal cord paralysis in association with familial hypertrophic polyneuropathy, and Plott relates three brothers with congenital laryngeal abductor paralysis caused by bilateral dysgenesis of the nucleus ambiguus. Bannister and Oppenheimer have called attention to defects of phonation and laryngeal stridor as early features of autonomic failure in multiple system atrophy (see Chap. 38). We have seen several such patients in whom stridor was a prominent feature of the illness, persisting in one patient for almost a year before other features of the degenerative disease became evident.


Neurology_Adams

Neurology_Adams. The vagus nerve may be implicated within the meninges by infectious, neoplastic, and inflammatory processes, within the medulla by vascular lesions (e.g., the lateral medullary syndrome of Wallenberg, as described in Chap. 33), and by motor neuron disease. Herpes zoster may attack this nerve, either alone or together with the ninth nerve as part of a jugular foramen syndrome. The vagus is often affected along with the glossopharyngeal nerve in spontaneous dissection of the carotid artery at the base of the skull. The nerves may be damaged in the course of thyroid surgery and may be involved in cases of advanced alcoholic or diabetic neuropathy. Finally, the vagus can be compressed by lesions of the jugular foramen as part of a multiple cranial nerve syndrome as summarized in Table 44-1; metastatic tumors such as from the prostate or breast and jugular vein thrombosis are typical causes.


Neurology_Adams

Neurology_Adams. A fact of some importance is that the left recurrent laryngeal nerve, because of its long course under the aortic arch, can become damaged as a result of lesions in the thorax. There is no dysphagia with lesions at this point in the nerve because the branches to the pharynx (but not to the larynx) have already been given off. For this reason, an aneurysm of the aortic arch, an enlarged left atrium, mediastinal lymph nodes from bronchial carcinoma, and a mediastinal or superior sulcus lung tumor are more frequent causes of an isolated (left) vocal cord palsy than are intracranial diseases. It is estimated that in one-quarter to one-third of all cases of paralysis of the recurrent laryngeal nerve no cause can be established, that is, they are idiopathic. The highest incidence is in the third decade, and males are more susceptible than females. Of the 21 cases reported by Blau and Kapadia, 5 recovered completely and 5 partially within a few months; no other disease appeared in the 8-year


Neurology_Adams

Neurology_Adams. decade, and males are more susceptible than females. Of the 21 cases reported by Blau and Kapadia, 5 recovered completely and 5 partially within a few months; no other disease appeared in the 8-year period that followed. Berry and Blair described palsies of the superior and recurrent laryngeal nerves, occurring as part of isolated vagal neuropathies. A few were bilateral and, again, the majority of the cases were idiopathic and had much the same prognosis as isolated palsies of the recurrent laryngeal nerve.


Neurology_Adams

Neurology_Adams. Laryngeal neuralgia is a rare entity in which paroxysms of pain are localized over the upper portion of the thyroid cartilage or hyoid bone on one or both sides. The pain may be evoked by coughing, yawning, talking, or sneezing. In the case reported by Brownstone and coworkers, the symptoms were relieved by carbamazepine. Neurologic Diagnosis of Vocal Cord Paralysis Clues from the history and examination can help determine the site of the lesion producing vocal cord palsy. If intramedullary, there are usually ipsilateral cerebellar signs, loss of pain and temperature sensation over the ipsilateral face and contralateral arm and leg, and an ipsilateral Bernard-Horner syndrome (see Table 33-3). If the lesion is extramedullary but intracranial, the glossopharyngeal and spinal accessory nerves are frequently involved as well (jugular foramen syndrome; see Table 44-1).


Neurology_Adams

Neurology_Adams. If extracranial in the posterior lateral condylar or retroparotid space, there may be a combination of ninth, tenth, eleventh, and twelfth cranial nerve palsies and a Horner syndrome. Combinations of these lower cranial nerve palsies, which have a variety of eponymic designations (see Table 44-1) are caused by various tumors, both primary and metastatic, or by chronic inflammations or granulomas involving lymph nodes at the base of the skull. If there is no palatal weakness and no pharyngeal or palatal sensory loss, the lesion is below the origin of the pharyngeal branches, which leaves the vagus nerve high in the cervical region. The usual site of disease is then the mediastinum. The Eleventh, or Spinal Accessory, Nerve


Neurology_Adams

Neurology_Adams. This is a purely motor nerve, of spinal rather than cranial origin. Its fibers arise from the anterior horn cells of the upper 4 or 5 cervical segments and enter the skull through the foramen magnum. Intracranially, the accessory nerve travels for a short distance with the part of the tenth nerve that is derived from the caudalmost cells of the nucleus ambiguus; together, the two roots are referred to as the vagal-accessory nerve or the cranial root of the accessory nerve. The 2 roots together leave the skull through the jugular foramen. The vagus fibers then rejoin the main trunk of the vagus. The motor fibers derived from the upper cervical segments of the spinal cord form an “external ramus” and innervate the ipsilateral sternocleidomastoid and trapezius muscles. Only the somatic motor fibers constitute the accessory nerve in the strict sense. In patients with torticollis, however, division of the upper cervical motor roots or the spinal accessory nerve has often failed to ablate


Neurology_Adams

Neurology_Adams. fibers constitute the accessory nerve in the strict sense. In patients with torticollis, however, division of the upper cervical motor roots or the spinal accessory nerve has often failed to ablate completely the contraction of the sternocleidomastoid muscle. This suggests a wider innervation of the muscle, perhaps by fibers of apparent vagal origin that join the accessory nerve for passage through the jugular foramen. The supranuclear innervation of the spinal accessory nuclei is apparently mainly ipsilateral as evidenced by contraversive turning of the head during a convulsion, the result of contraction of the ipsilateral sternocleidomastoid muscle. Whether this is attributable to a direct ipsilateral tract, or to double crossing of the supranuclear tracts, is not known.


Neurology_Adams

Neurology_Adams. A complete lesion of the accessory nerve results in weakness of the sternocleidomastoid muscle and upper part of the trapezius (the lower part of the trapezius is innervated by the third and fourth cervical roots through the cervical plexus). Weakness of the sternocleidomastoid can be demonstrated by having the patient forcibly turn the head in the opposite direction against the examiner’s hand. When it is weak, little force will be generated and the examiner will feel that the sternocleidomastoid does not contract firmly beneath the fingers. This muscle can be further tested by having the patient press his head forward against resistance or lift his head from the pillow. Weakness of the trapezius can be demonstrated by asking the patient to shrug his shoulders; the affected side will be found to be weaker, and there will often be evident atrophy of the upper part of the trapezius. With the arms at the sides, the shoulder on the affected side droops and the scapula is slightly winged;


Neurology_Adams

Neurology_Adams. to be weaker, and there will often be evident atrophy of the upper part of the trapezius. With the arms at the sides, the shoulder on the affected side droops and the scapula is slightly winged; the latter defect is accentuated with lateral movement of the arm (with serratus anterior weakness, winging of the scapula is more prominent and occurs on forward elevation of the arm).


Neurology_Adams

Neurology_Adams. Motor neuron disease, poliomyelitis, syringomyelia, and spinal cord tumors may involve neurons of the spinal accessory nerve. In its intracranial portion, the nerve is usually affected along with the ninth and tenth cranial nerves by herpes zoster or by lesions of the jugular foramen (glomus tumors, neurofibromas, metastatic carcinoma, internal jugular vein thrombosis). Tumors at the foramen magnum may also damage the nerve. In the posterior triangle of the neck, the eleventh nerve can be damaged during surgical operations and by external compression or injury. Compressive and invasive lesions of the nerve may be visualized by CT or MRI of the posterior cervical space.


Neurology_Adams

Neurology_Adams. A benign disorder of the eleventh nerve, akin to Bell’s palsy, has been described by Spillane and by Eisen and Bertrand. It begins with pain in the low lateral neck that subsides in a few days and is followed by weakness and atrophy in the distribution of the nerve. Also, a recurrent form of spontaneous accessory neuropathy has been described (Chalk and Isaacs). About one-quarter to one-third of eleventh nerve lesions are estimated to be of this idiopathic type; most, but not all, of the patients recover. Bilateral sternocleidomastoid and trapezius palsy, which occurs with primary disease of muscles—for example, polymyositis and muscular dystrophy—may be difficult to distinguish from a bilateral damage to the accessory nerves or the motor nuclei (progressive bulbar palsy). The Twelfth, or Hypoglossal, Nerve


Neurology_Adams

Neurology_Adams. This is also a pure motor nerve, which supplies the somatic musculature of the tongue. It arises as a series of rootlets that issue from the ventral medulla between the pyramid and inferior olivary complex. The nerve leaves the skull through the hypoglossal foramen and innervates the genioglossus muscle, which acts to protrude the tongue; the styloglossus, which retracts and elevates its root; and the hypoglossus, which causes the upper surface to become convex. Complete interruption of the nerve results in paralysis of one side of the tongue. The tongue curves slightly to the healthy side as it lies in the mouth, but on protrusion it deviates to the affected side, owing to the unopposed contraction of the healthy genioglossus muscle. By pushing against the patient’s tongue in the cheek, one can judge the degree of weakness. Patients with lesions of the hypoglossal nerve will have difficulty moving the tongue with natural facility, causing difficulty with handling food in the mouth as


Neurology_Adams

Neurology_Adams. can judge the degree of weakness. Patients with lesions of the hypoglossal nerve will have difficulty moving the tongue with natural facility, causing difficulty with handling food in the mouth as well as lingual dysarthria. Over time, the denervated side becomes wrinkled and atrophied, and fasciculations become apparent.


Neurology_Adams

Neurology_Adams. Isolated lesions of the hypoglossal nerve roots are rare. Occasionally an intramedullary lesion, usually a stroke, damages the emerging fibers of the hypoglossal nerve, corticospinal tract, and medial lemniscus (see Table 33-3). The result is paralysis and atrophy of one side of the tongue, together with spastic paralysis and loss of vibration and position sense in the opposite arm and leg. Poliomyelitis and motor neuron disease may destroy the hypoglossal nuclei. The latter is the most common cause of a bilaterally atrophic and fasciculating tongue. Lesions of the basal meninges and of the occipital bones (tumor invasion, platybasia, invagination of the occipital condyles, Paget disease) may involve the nerve in its extramedullary course, and it is sometimes damaged in operations on the neck including carotid endarterectomy. Goodman and coworkers showed a dissecting aneurysm of the carotid artery to have compressed the hypoglossal nerve, with resultant weakness and atrophy of the


Neurology_Adams

Neurology_Adams. neck including carotid endarterectomy. Goodman and coworkers showed a dissecting aneurysm of the carotid artery to have compressed the hypoglossal nerve, with resultant weakness and atrophy of the tongue. Rare instances of temporal arteritis and Takayasu arteritis affecting the carotid artery and adjacent twelfth nerve have been described. Lance and Anthony have described the simultaneous occurrence of nuchal-occipital pain and ipsilateral numbness of the tongue, provoked by the sudden, sharp turning of the head and termed it the neck–tongue syndrome. The phenomenon has been attributed to compression in the atlantoaxial space of the second cervical root, which carries some of the sensory fibers from the tongue, via the hypoglossal nerve, to the C2 segment of the spinal cord.


Neurology_Adams

Neurology_Adams. It is worth mentioning here that the tongue is often red and smooth in vitamin-deficiency states. Glossodynia (burning mouth syndrome discussed in Chap. 9), a condition most frequently seen in the elderly and in young women, may or may not be accompanied by redness and dryness, but not by lingual weakness. A habit of tongue-thrusting and teeth-clenching is often associated. The ascription of these motor abnormalities to a psychogenic mechanism does not agree with the authors’ experience (see Quinn).


Neurology_Adams

Neurology_Adams. This syndrome is the result of weakness or paralysis of muscles that are supplied by the motor nuclei of the lower brainstem, that is, the motor nuclei of the fifth, seventh, and ninth to twelfth cranial nerves. (Strictly speaking, the motor nuclei of the fifth and seventh nerves lie outside the “bulb,” which is the old name for the medulla oblongata.) Involved are the muscles of the jaw and face; the sternocleidomastoids and upper parts of the trapezii; and the muscles of the tongue, pharynx, and larynx. If weakness develops rapidly, as may happen in GBS, diphtheria, or poliomyelitis, there is no time for muscle atrophy. Myasthenia gravis, inclusion body myopathy, and polymyositis on rare occasions may produce such a picture, but motor neuron disease is the most common cause. When the latter disease is isolated to the bulbar muscles, it has been called progressive bulbar palsy, as discussed in Chap. 38. This can also be a presentation of Kennedy bulbospinal atrophy. The chronic forms


Neurology_Adams

Neurology_Adams. disease is isolated to the bulbar muscles, it has been called progressive bulbar palsy, as discussed in Chap. 38. This can also be a presentation of Kennedy bulbospinal atrophy. The chronic forms of motor neuron disease and the childhood form of Fazio-Londe disease result in marked wasting and fasciculation of the facial, tongue, sternocleidomastoid, and trapezius muscles. All of these disorders must be differentiated from pseudobulbar palsy that is discussed in Chaps. 24 and 25.


Neurology_Adams

Neurology_Adams. As one can readily understand, several cranial nerves may be affected by a single disease process. The first clinical problem that arises is whether the lesion lies within or outside the brainstem. Lesions lying on the surface of the brainstem, infiltrating the meninges, or situated at the base of the skull are characterized by involvement of adjacent cranial nerves (often occurring in succession) and by late and only slight, if any, involvement of the long sensory and motor pathways. These syndromes are discussed later and listed in Table 44-1 by their eponymic designations. The opposite is true of intramedullary, intrapontine, and intramesencephalic lesions; within the brainstem that involve cranial nerves and produce crossed sensory or motor paralysis (cranial nerve signs on one side of the body and tract signs on the opposite side, the historical aspects of which are reviewed by Silverman et al). In this way, a number of distinctive brainstem syndromes, to which eponyms have also


Neurology_Adams

Neurology_Adams. the body and tract signs on the opposite side, the historical aspects of which are reviewed by Silverman et al). In this way, a number of distinctive brainstem syndromes, to which eponyms have also been attached, are produced; these are listed in Table 33-5 because they are most often the result of brainstem stroke. The special problems of multiple cranial nerve palsies of the ocular motor nerves are addressed in Chap. 13.


Neurology_Adams

Neurology_Adams. Involvement of multiple cranial nerves outside the brainstem may be the result of trauma; localized infections such as herpes zoster (subacute onset); Lyme disease as reported by Schmutzhard and colleagues; cytomegalovirus (CMV) infection in an HIV patient; Wegener granulomatosis, sarcoidosis, other types of granulomatous diseases, or compression by tumors and saccular aneurysms. The sequential painless affection of contiguous or noncontiguous nerves over several days or weeks is particularly characteristic of meningeal carcinomatosis or lymphomatosis. In the series of 79 cases accumulated by Keane (2005), tumor was by far the most common underlying cause of multiple cranial nerve palsies— particularly schwannomas, metastases, and meningiomas; trauma, infection, and vascular disease followed in frequency after neoplasm. The eighth nerve is commonly incorporated in these neoplastic meningeal infiltrations. Among the solid tumors that cause local compression of nerves, neurofibromas,


Neurology_Adams

Neurology_Adams. in frequency after neoplasm. The eighth nerve is commonly incorporated in these neoplastic meningeal infiltrations. Among the solid tumors that cause local compression of nerves, neurofibromas, schwannomas, meningiomas, cholesteatomas, carcinomas, chordomas, and chondromas have all been observed. Nasopharyngeal carcinoma (Schmincke tumor or lymphoepithelioma) may implicate several cranial nerves in succession by invading the base of the skull (mainly the fifth and sixth but also higher nerves;


Neurology_Adams

Neurology_Adams. Fig. 44-5), as do basilar invagination and Chiari malformation. Several lower cranial nerves may be involved on one side by a carotid artery dissection. A successive involvement of all cranial nerves on one side has been referred to as Garcin syndrome, or hemibasal syndrome. It has been reported in chondromas and chondrosarcomas of the clivus, but may occur with nasopharyngeal carcinomas. Bone erosion is likely to be seen radiographically in these cases. Table 44-2 lists the main causes of multiple cranial nerve palsies of extramedullary origin in our experience.


Neurology_Adams

Neurology_Adams. The question of viral infections of cranial nerves is always raised by acute neuropathies of the facial, trigeminal, and vestibulocochlear nerves, especially when the condition is bilateral, involves several nerves in combination, or is associated with a pleocytosis in the spinal fluid. Actually, the only proved viral etiologies in this group of cases are herpes simplex, herpes zoster, and cytomegalovirus infections. Because neural deafness, vertigo, and other cranial nerve palsies have been observed in conjunction with the postinfectious encephalomyelitides of


Neurology_Adams

Neurology_Adams. Mycoplasma, varicella, measles, rubella, mumps, and scarlet fever, they probably share an immune-mediated mechanism. Multiple or single cranial nerve palsies of abrupt onset may precede or accompany infectious mononucleosis and sometimes other viral or mycoplasmal diseases. DeSimone and Snyder assembled a series of 20 such cases associated with mononucleosis; bilateral facial paralysis was the most common presentation, bilateral optic neuritis the next most common, and in 3 cases, 3 or 4 cranial nerves were involved. The prognosis is excellent.


Neurology_Adams

Neurology_Adams. Some cases formerly thought to be postinfectious in nature may be true infections of the nerve. The same may be said of the single and multiple cranial nerve palsies that are sometimes associated with HIV and CMV infections. Treatment of the parainfectious cases is symptomatic; the prognosis for recovery is good in many cases. Quite often one observes an acute or subacute form of multiple cranial neuropathy of undetermined cause. Juncos and Beal reported on 14 cases of this type, incorporating 6 well-documented cases of the Tolosa-Hunt orbitocavernous sinus syndrome with oculomotor palsies. In the group that was not attributable to Tolosa-Hunt, the onset was with facial pain and headache (temporofrontal), followed within days by abducens palsy (12 of 14), oculomotor palsy (6 of 14), trigeminal palsy (5 of 14), and facial weakness (4 of 14), and less often by involvement of the eighth, ninth, and tenth cranial nerves (unilaterally in most instances). Increased CSF protein and


Neurology_Adams

Neurology_Adams. trigeminal palsy (5 of 14), and facial weakness (4 of 14), and less often by involvement of the eighth, ninth, and tenth cranial nerves (unilaterally in most instances). Increased CSF protein and pleocytosis occurred in several. The prompt relief of pain upon administration of steroids was similar to that obtained in the Tolosa-Hunt syndrome. The mode of recovery, which usually occurred within a few months, was also much the same in the 2 groups of patients. Juncos and Beal concluded that the clinical features of the 2 groups overlapped and that their separation into 2 syndromes was arbitrary. We have seen a relapsing form of this illness in young adults, responsive on each occasion to steroids and stabilizing after several years. Numerous tests of the CSF by polymerase chain reaction revealed no viruses. Conceivably, some of these cases represent variant forms of GBS, in as much as they may be preceded by a nonspecific infection and may at times be accompanied by areflexia or


Neurology_Adams

Neurology_Adams. revealed no viruses. Conceivably, some of these cases represent variant forms of GBS, in as much as they may be preceded by a nonspecific infection and may at times be accompanied by areflexia or evanescent paresthesias and elevated CSF protein without pleocytosis. Others probably are examples of the entity described by Juncos and Beal, possibly reflecting a granulomatous process in the pachymeninges.


Neurology_Adams

Neurology_Adams. As a more chronic affliction, we have observed numerous cases in which cranial nerves were affected sequentially over a period of many years (polyneuritis cranialis multiplex). Two were later found to have tuberculosis of cervical lymph nodes (presumably tuberculous scrofula), and 3 had sarcoidosis. No cause was determined in the rest. Symonds had similar experience. It is usually worth obtaining a biopsy of an enlarged cervical lymph node in these circumstances.


Neurology_Adams

Neurology_Adams. The cavernous sinus syndrome, discussed in Chaps. 31, 33, and elsewhere in the book, consists of various combinations of oculomotor palsies and upper trigeminal sensory loss, usually accompanied by signs of increased pressure or inflammation of the venous sinus. The third, fourth, fifth, and sixth cranial nerves are affected first on one side only, but any of the processes that infiltrate or obstruct the sinus may spread to the other side. The main causes are septic or aseptic thrombosis of the venous sinus due to trauma, hypercoagulable states, or adjacent infections in adjacent structures, carotid artery aneurysm, carotid-cavernous fistulae, and neoplastic infiltration. Keane (1996) summarized his experience with an astonishing 151 instances of cavernous sinus syndrome and found trauma and surgical procedures to be the most common causes, followed by neoplasms (specifically those originating in the nasopharynx), pituitary tumors, metastases, and lymphomas; our experience has tended


Neurology_Adams

Neurology_Adams. and surgical procedures to be the most common causes, followed by neoplasms (specifically those originating in the nasopharynx), pituitary tumors, metastases, and lymphomas; our experience has tended more toward local infectious causes in diabetic patients and hypercoagulable states.


Neurology_Adams

Neurology_Adams. A special cause of multiple cranial nerve palsies is an infiltration along the distal nerves in the skin and subcutaneous tissues by squamous cell carcinomas of the face, especially by spindle cell and other atypical varieties of tumor. A variant of malignant melanoma, “lentigo maligna” may do the same but has more of a tendency to infiltrate along larger nerves to the base of the skull and cause larger areas of loss of facial sensation and pain, vertigo, and deafness. This type of perineural spread first causes very restricted unilateral palsies and sensory loss related to the superficial branches of the fifth and seventh cranial nerves in one region of the face and then extends to the base of the skull and to the ventral brainstem. According to Clouston and colleagues, who have presented 5 cases in detail, the initial symptoms are usually pain and numbness in the area underlying the skin lesion and facial weakness confined to the same regions of the face; this pattern is a result of


Neurology_Adams

Neurology_Adams. 5 cases in detail, the initial symptoms are usually pain and numbness in the area underlying the skin lesion and facial weakness confined to the same regions of the face; this pattern is a result of the proximity of fifth and seventh nerve branches in the skin and subcutaneous tissues. Various combinations of oculomotor palsies may follow as a result of tumor entry into the orbit via the infraorbital branch of the maxillary nerve. Occasionally there is no pain. We have also observed a similar regional pattern of extracranial involvement of trigeminal and facial nerves with an infiltrative mixed-cell tumor of the parotid gland.


Neurology_Adams

Neurology_Adams. Alexander GE, Moses H: Carbamazepine for hemifacial spasm. Neurology 32:286, 1982. Bannister R, Oppenheimer DR: Degenerative diseases of the nervous system associated with autonomic failure. Brain 95:457, 1972. Baringer JH: Herpes simplex virus and Bell palsy. Ann Intern Med 124:63, 1996. Barker FG, Jannetta PJ, Bissonette DJ, et al: Microvascular decompression for hemifacial spasm. J Neurosurg 82:201, 1995. Berry H, Blair RL: Isolated vagus nerve palsy and vagal mononeuritis. Arch Otolaryngol 106:333, 1980. Blau JN, Harris M, Kennet S: Trigeminal sensory neuropathy. N Engl J Med 281:873, 1969. Blau JN, Kapadia R: Idiopathic palsy of the recurrent laryngeal nerve: A transient cranial mononeuropathy. Br Med J 4:259, 1972. Brownstone PK, Ballenger JJ, Vick NA: Bilateral superior laryngeal neuralgia. Arch Neurol 37:525, 1980.


Neurology_Adams

Neurology_Adams. Brownstone PK, Ballenger JJ, Vick NA: Bilateral superior laryngeal neuralgia. Arch Neurol 37:525, 1980. Burgess RC, Michaels L, Bale JF Jr, Smith RJ: Polymerase chain reaction amplification of herpes simplex viral DNA from the geniculate ganglion of a patient with Bell’s palsy. Ann Otol Rhinol Laryngol 103:775, 1994. Chalk C, Isaacs H: Recurrent spontaneous accessory neuropathy. J Neurol Neurosurg Psychiatry 53:621, 1990. Chia L-G: Pure trigeminal motor neuropathy. BMJ 296:609, 1988. Clouston PD, Sharpe DM, Corbett AJ, et al: Perineural spread of cutaneous head and neck cancer: Its orbital and central neurologic complications. Arch Neurol 47:73, 1990. De Diego JI, Prim MP, De Sarria MJ, et al: Idiopathic facial paralysis: A randomized, prospective, and controlled study using single-dose prednisone versus acyclovir three times daily. Laryngoscope 108:573, 1998. DeSimone PA, Snyder D: Hypoglossal nerve palsy in infectious mononucleosis. Neurology 28:844, 1978.


Neurology_Adams

Neurology_Adams. DeSimone PA, Snyder D: Hypoglossal nerve palsy in infectious mononucleosis. Neurology 28:844, 1978. Eisen A, Bertrand G: Isolated accessory nerve palsy of spontaneous origin: A clinical and electromyographic study. Arch Neurol 27:496, 1972. Elias MK, Mateen FJ, Weller CR, et al: The Melkersson-Rosenthal syndrome: A retrospective series of biopsied cases. J Neurol 260:138, 2013. Engstrom M, Berg T, et al: Prednisolone and valaciclovir in Bell’s palsy: A randomised, double-blind, placebo-controlled, multicentre trial. Lancet Neurol 7(11):993–1000, 2008. Gilden DH: Bell’s palsy. N Engl J Med 351:1323, 2004. Goodman JM, Zink WL, Cooper DF: Hemilingual paralysis caused by spontaneous carotid artery dissection. Arch Neurol 40:653, 1983. Granit R, Leskell L, Skogland CR: Fibre interaction in injured or compressed region of nerve. Brain 67:125, 1944.


Neurology_Adams

Neurology_Adams. Granit R, Leskell L, Skogland CR: Fibre interaction in injured or compressed region of nerve. Brain 67:125, 1944. Hato N, Yamada H, Kohno H: Valacyclovir and prednisolone treatment for Bell’s palsy: a multicenter, randomized, placebo-controlled study. Otol Neurotol 28(3):408–413, 2007. Hauser WA, Karnes WE, Annis J, Kurland LT: Incidence and prognosis of Bell’s palsy in the population of Rochester, Minnesota. Mayo Clin Proc 46:258, 1971. Hosten N: MR of brain involvement in progressive facial hemiatrophy (Romberg disease): Reconsideration of a syndrome. AJNR Am J Neuroradiol 15:145, 1994. Hughes RAC: Diseases of the fifth cranial nerve. In: Dyck PJ, Thomas PK, Lambert EH, et al (eds): Peripheral Neuropathy, 3rd ed. Philadelphia, Saunders, 1993, pp 801–817. Illingworth RD, Porter DG, Jakubowski J: Hemifacial spasm: A prospective long-term follow up of 83 patients treated by microvascular decompression. J Neurol Neurosurg Psychiatry 60:73, 1996.


Neurology_Adams

Neurology_Adams. Illingworth RD, Porter DG, Jakubowski J: Hemifacial spasm: A prospective long-term follow up of 83 patients treated by microvascular decompression. J Neurol Neurosurg Psychiatry 60:73, 1996. Jannetta PJ: Posterior fossa neurovascular compression syndromes other than neuralgias. In: Wilkins RH, Rengachary SS (eds): Neurosurgery, 2nd ed. New York, McGraw-Hill, 1996, pp 3227–3233. Johnson JA, Stern LZ: Bilateral vocal cord paralysis in a patient with familial hypertrophic neuropathy. Arch Neurol 38:532, 1981. Johnson VP, McMillin JM, Aceto T, Bruins G: A newly recognized neuroectodermal syndrome of familial alopecia, anosmia, deafness, and hypogonadism. Am J Med Genet 15:497, 1983. Juncos JL, Beal MF: Idiopathic cranial polyneuropathy. Brain 110:197, 1987. Karnes WE: Diseases of the seventh cranial nerve. In: Dyck PJ, Thomas PK, Lambert EH, et al (eds): Peripheral Neuropathy, 3rd ed. Philadelphia, Saunders, 1993, pp 818–836.


Neurology_Adams

Neurology_Adams. Karnes WE: Diseases of the seventh cranial nerve. In: Dyck PJ, Thomas PK, Lambert EH, et al (eds): Peripheral Neuropathy, 3rd ed. Philadelphia, Saunders, 1993, pp 818–836. Katusic S, Beard CM, Bergstralh E, Kurland LT: Incidence and clinical features of trigeminal neuralgia, Rochester, Minnesota, 1945–1984. Ann Neurol 27:89, 1990. Keane JR: Bilateral seventh nerve palsy: Analysis of 43 cases and review of the literature. Neurology 44:1198, 1994. Keane JR: Cavernous sinus syndrome: Analysis of 151 cases. Arch Neurol 53:967, 1996. Keane JR: Multiple cranial nerve palsies: Analysis of 79 cases. Arch Neurol 62:1714, 2005. Kress B, Griesbeck F, Stippich C, et al: Bell’s palsy: Quantitative analysis of MR imaging data as a method of predicting outcome. Radiology 230:504, 2004. Lance JW, Anthony M: Neck-tongue syndrome on sudden turning of the head. J Neurol Neurosurg Psychiatry 43:97, 1980. Lecky BRF, Hughes RAC, Murray NMF: Trigeminal sensory neuropathy. Brain 110:1463, 1987.


Neurology_Adams

Neurology_Adams. Lecky BRF, Hughes RAC, Murray NMF: Trigeminal sensory neuropathy. Brain 110:1463, 1987. Love S, Coakham HB: Trigeminal neuralgia. Pathology and pathogenesis. Brain 124:2347, 2001. Massey EW, Moore J, Schold SC Jr: Mental neuropathy from systemic cancer. Neurology 31:1277, 1981. Murakami S, Honda N, Mizobuchi M, et al: Rapid diagnosis of varicella zoster virus in acute facial palsy. Neurology 51:1202, 1998. Murakami S, Mizobuchi M, Nakashiro Y, et al: Bell palsy and herpes simplex virus: Identification of viral DNA in endoneurial fluid and muscle. Ann Intern Med 124:27, 1996. Nielsen VK, Jannetta PJ: Pathophysiology of hemifacial spasm: Effects of facial nerve decompression. Neurology 34:891, 1984. Piatt JH, Wilkins RH: Treatment of tic douloureux and hemifacial spasm by posterior fossa exploration: Therapeutic implications of various neurovascular relationships. Neurosurgery 14:462, 1984.


Neurology_Adams

Neurology_Adams. Piatt JH, Wilkins RH: Treatment of tic douloureux and hemifacial spasm by posterior fossa exploration: Therapeutic implications of various neurovascular relationships. Neurosurgery 14:462, 1984. Pitts DB, Adour KK, Hilsinger RL: Recurrent Bell’s palsy analysis of 140 patients. Laryngoscope 98:535, 1988. Plott D: Congenital laryngeal-abductor paralysis due to nucleus ambiguus dysgenesis in three brothers. N Engl J Med 271:593, 1964. Quinn JH: Glossodynia. J Am Dent Assoc 70:1418, 1965. Resnick DK, Jannetta PJ, Bissonette D, et al: Microvascular decompression for glossopharyngeal neuralgia. Neurosurgery 36:64, 1995. Schmutzhard E, Stanek G, Pohl P: Polyneuritis cranialis associated with Borrelia burgdorferi. J Neurol Neurosurg Psychiatry 48:1182, 1985. Silverman JE, Liu GT, Volpe NJ, Galetta SL: The crossed paralyses. Arch Neurol 52:635, 1995. Spillane JD: Isolated unilateral spinal accessory nerve palsy of obscure origin. Br Med J 2:365, 1949.


Neurology_Adams

Neurology_Adams. Silverman JE, Liu GT, Volpe NJ, Galetta SL: The crossed paralyses. Arch Neurol 52:635, 1995. Spillane JD: Isolated unilateral spinal accessory nerve palsy of obscure origin. Br Med J 2:365, 1949. Spillane JD, Wells CEC: Isolated trigeminal neuropathy: A report of 16 cases. Brain 82:391, 1959. Sullivan FM, Swan IR, Donnan PR, et al: Early treatment with prednisolone or acyclovir in Bell’s palsy. N Engl J Med 357:1598, 2007. Sweeney CJ, Gilden DH: Ramsay Hunt syndrome. J Neurol Neurosurg Psychiatry 71:149, 2001. Symonds C: Recurrent multiple cranial nerve palsies. J Neurol Neurosurg Psychiatry 21:95, 1958. van Amstel AD, Devriese PP: Clinical experience with recurrences of Bell’s palsy. Arch Otorhinolaryngol 245:302, 1998. Whitley RJ, Weiss H, Gnann JW, et al: Acyclovir with and without prednisone for the treatment of herpes zoster: A randomized, placebo-controlled trial. Ann Intern Med 125:376, 1996.


Neurology_Adams

Neurology_Adams. Whitley RJ, Weiss H, Gnann JW, et al: Acyclovir with and without prednisone for the treatment of herpes zoster: A randomized, placebo-controlled trial. Ann Intern Med 125:376, 1996. Wilson ME, Hoxie J: Facial asymmetry in superior oblique muscle palsy. J Pediatr Ophthalmol Strabismus 30:315, 1993. Figure 44-1. Scheme of the trigeminal nuclei and some of the trigeminal reflex arcs. I, ophthalmic division; II, maxillary division; III, mandibular division. (Originally from Ramon y Cajal S: La Textura del Sistema Nervista del Hombre y los Vertebrados, Madrid, Moya, as adapted from Carpenter MB, Sutin J: Human Neuroanatomy, 8th ed. Baltimore, Williams & Wilkins, 1982, by permission.) Figure 44-2. Left-sided facial sensory loss due to demyelination of the trigeminal root entry zone in a patient with multiple sclerosis. Abnormal enhancement of the nerve root is seen on T1 postgadolinium MRI.


Neurology_Adams

Neurology_Adams. Nucleus fasc.solitariusGeniculateganglionChordatympaniNasal andpalatineglandsLacrimalglandTrigeminalganglionMajor superficialpetrosal nerveIIIIIILingual nerveSubmandibular gang.Submandibular glandPterygopalatineganglionSublingualglandCBAMotor rootN. VIIFasc. solitariusMotor nucleusN. VIISup. salivatorynucleusVI Figure 44-3. Scheme of the seventh cranial (facial) nerve. The motor fibers are represented by the solid purple line originating in the motor nucleus of VII. Parasympathetic fibers are represented by regular dashes; special visceral afferent (taste) fibers are represented by long dashes and dots. A, B, and C denote lesions of the facial nerve at the stylomastoid foramen, distal to the geniculate ganglion, and proximal to the geniculate ganglion. Disturbances resulting from lesions at each of these sites are described in the text. (From Carpenter MB, Sutin J: Human Neuroanatomy, 8th ed. Baltimore, Williams & Wilkins, 1982, by permission.)


Neurology_Adams

Neurology_Adams. Figure 44-4. Anatomic features of the vagus nerve. Note the relationship to the spinal- accessory and glossopharyngeal nerves at the jugular foramen and the long course of the left recurrent laryngeal nerve, which is longer than the right and hooks around the aortic arch (not shown). Figure 44-5. Nasopharyngeal carcinoma invading the anterior left side of the base of the skull and nasopharynx and causing third and fifth nerve palsies. Axial CT of the anterior skull base. Chapter 44 Diseases of the Cranial Nerves Motor nucleusN. VMotor nucleusN. VIINucleus N. XIINucleus spinal VMotor rootfibersSecondary tri-geminal fibersSpinal VIIIIIIGasserianganglionMesencephalic nucleusPrincipal sensorynucleus


Neurology_Adams

Neurology_Adams. Motor nucleusN. VMotor nucleusN. VIINucleus N. XIINucleus spinal VMotor rootfibersSecondary tri-geminal fibersSpinal VIIIIIIGasserianganglionMesencephalic nucleusPrincipal sensorynucleus Distal vagusEsophageal plexusEsophageal hiatusof diaphragmSuperior cardiac ramiInferior cardiac ramiPulmonary branchesAnterior and posteriorvagus nervesRecurrent laryngeal n.Cervical vagusInt. jugular v.Int. carotid a.(Muscles and mucosa ofpharnyx, soft palate) (Mucosa and glands oflarnyx and epiglottis)Trachea and esophagusLaryngeal muscles(Cricothyroid m) Glossopharyngeal n.Meningeal br.Auricular br.Vagus n.Spinal accessory n.Jugular foramenJugular ganglionNodose ganglionDorsal motor nucleus of vagusNucleus ambiguusPharyngeal branchSuperior laryngeal br Diseases of Muscle


Neurology_Adams

Neurology_Adams. Diseases of Muscle Skeletal, or voluntary, muscle constitutes the principal organ of motion, as well as a vast metabolic reservoir. Disposed in more than 600 separate muscles, this tissue makes up as much as 40 percent of the weight of adult human beings. An intricacy of structure and function undoubtedly accounts for its diverse susceptibility to disease, for which reason the main anatomic and clinical facts are provided as an introduction to the muscle diseases.


Neurology_Adams

Neurology_Adams. A single muscle is composed of thousands of muscle fibers that extend for variable distances along its longitudinal axis. Each fiber is a relatively large and complex multinucleated cell varying in length from a few millimeters to several centimeters (34 cm in the human sartorius muscle) and in diameter from 10 to 100 µm. Some fibers span the entire length of the muscle; others are joined end to end by connective tissue. Each muscle fiber is enveloped by an inner plasma membrane (the sarcolemma) and an outer basement membrane. The multiple nuclei of each fiber, which are oriented parallel to its longitudinal axis and may number in the thousands, lie beneath the plasma membrane (sarcolemma); hence they are termed subsarcolemmal, or sarcolemmal nuclei.


Neurology_Adams

Neurology_Adams. The cytoplasm (sarcoplasm) of the cell is abundant, and it contains myofibrils and various organelles such as mitochondria and ribosomes. Each myofibril is enveloped in a membranous net, the sarcoplasmic reticulum (SR; Fig. 45-1). Extensions of the plasma membrane into the fiber form the transverse tubular system (T tubules), which are extracellular channels of communication with the intracellular sarcoplasmic reticulum. The SR and T tubules are anatomically independent but functionally related membrane systems. The junctional gap between the T tubules and SR is occupied by protein formations that are attached to the SR and are referred to as junctional feet; the latter have been identified as ryanodine receptors and are responsible for the release of calcium from the SR, which is a critical step in exciting the muscle (see Franzini-Armstrong).


Neurology_Adams

Neurology_Adams. The myofibrils themselves are composed of longitudinally oriented interdigitating filaments (myofilaments) of contractile proteins (actin and myosin), additional structural proteins (titin and nebulin), and regulatory proteins (tropomyosin and troponin). The series of biochemical events by which these proteins, under the influence of calcium ions, accomplish the contraction and relaxation of muscle is described in Chap. 2. Droplets of stored fat, glycogen, various proteins, many enzymes, and myoglobin, the latter imparting the red color to muscle, are contained within the sarcoplasm or its organelles.


Neurology_Adams

Neurology_Adams. The individual muscle fibers are surrounded by delicate strands of connective tissue (endomysium), which provide their support and permit unity of action. Capillaries, of which there may be several for each fiber, and nerve fibers lie within the endomysium. Muscle fibers are bound into groups or fascicles by sheets of collagen (perimysium), which also bind together groups of fascicles and surround the entire muscle (epimysium). The latter connective tissue tunics are richly vascularized, different types of muscle having different arrangements of arteries and veins. The muscle fibers are attached at their ends to tendon fibers, which, in turn, connect with the skeleton. By this means, muscle contraction maintains posture and imparts movement.


Neurology_Adams

Neurology_Adams. Other notable characteristics of muscle are its natural mode of contraction, that is, through neural innervation—and the necessity of intact innervation for the maintenance of its normal tone and trophic state. Each muscle fiber receives a nerve twig from a motor nerve cell in the anterior horn of the spinal cord or nucleus of a cranial nerve; the nerve twig joins the muscle fiber at the neuromuscular junction or motor endplate. As was pointed out in Chaps. 2 and 3, groups of muscle fibers with a common innervation from one anterior horn cell constitute the motor unit, which is the basic physiologic unit in all reflex, postural, and voluntary activities.


Neurology_Adams

Neurology_Adams. Embedded in the surface membrane are several types of ion channels that are responsible for maintaining the electrical potential and propagating depolarizing currents across the muscle membrane. Diseases of these channels are discussed in Chap. 46. Also constituting a large part of the membrane is a series of anchoring structural proteins, the nature of which have been thoroughly elucidated in the past few decades. These are described in detail in relation to the muscular dystrophies.


Neurology_Adams

Neurology_Adams. In addition to motor nerve endings, muscle contains several types of sensory endings, all of them mechanoreceptors: Free nerve endings subserve the sensation of deep pressure-pain; Ruffini and pacinian corpuscles are pressure sensors; and the Golgi tendon organs and muscle spindles are tension receptors and participate in the maintenance of muscle tone and reflex activity. The Golgi receptors are located mainly at the myotendon junctions; pacinian corpuscles are localized in the tendon but are also found sparsely in muscle itself. Muscle spindles are specialized groups of small muscle fibers that regulate muscle contraction and relaxation, as described in Chap. 2. All of these receptors are present in the highest density in muscles that are involved in fine movements.


Neurology_Adams

Neurology_Adams. Muscles are not equally susceptible to disease, despite the apparent similarity of their structure. In fact, practically no disease affects all muscles in the body and each pathologic entity has a characteristic topography within the musculature. The topographic differences between diseases provide incontrovertible evidence of structural or physiologic differences between muscles that are not presently disclosed by the light or electron microscope. The factors responsible for the selective vulnerability of certain muscles are not known but several hypothetical explanations come to mind. One may relate simply to fiber size; consider, for example, the large diameter and length of the fibers of the glutei and paravertebral muscles in comparison with the smallness of the ocular muscle fibers. The number of fibers composing a motor unit may also be of significance; in the ocular muscles, a motor unit contains only 6 to 10 muscle fibers (some even fewer), but a motor unit of the


Neurology_Adams

Neurology_Adams. fibers. The number of fibers composing a motor unit may also be of significance; in the ocular muscles, a motor unit contains only 6 to 10 muscle fibers (some even fewer), but a motor unit of the gastrocnemius contains as many as 1,800 fibers. Also, the eye muscles have a much higher metabolic rate and a richer content of mitochondria than the large trunk muscles. Differences in patterns of vascular supply may permit some muscles to withstand the effects of vascular occlusion better than others. Histochemical studies of skeletal muscles have disclosed that within any 1 muscle, there are subtle metabolic differences between fibers, certain ones (type 1 fibers) being richer in oxidative and poorer in glycolytic enzymes and others (type 2 fibers) having the opposite distribution. The distribution of certain structural proteins may alter the topography of disease expression; for example, the eye muscles do not contain dystrophin, a submembrane protein that is deficient in Duchenne


Neurology_Adams

Neurology_Adams. distribution of certain structural proteins may alter the topography of disease expression; for example, the eye muscles do not contain dystrophin, a submembrane protein that is deficient in Duchenne muscular dystrophy, which explains the muscles’ lack of involvement in this disease. The endomysial fibroblasts of eye muscles contain an abundance of glycosaminoglycans, which renders them susceptible to thyroid diseases. Diseases of the neuromuscular junction show a distribution of weakness in relation to the density of these junctions in different muscles. Doubtless other differences will be discovered.


Neurology_Adams

Neurology_Adams. Normal muscle is endowed with a population of embryonic muscle precursor cells, known as satellite cells, and, as a result, it possesses a remarkable capacity to regenerate, a point often forgotten. It has been estimated that enough new muscle can be generated from a piece of normal muscle the size of a pencil eraser to provide normal musculature for a 70-kg adult. However, with complete destruction of the muscle fiber, this regenerative capacity is greatly impaired. Inflammatory and metabolic destructive processes are usually followed by fairly complete restoration of the muscle cells, provided that some part of each fiber has survived and the endomysial sheaths of connective tissue have not been severely disrupted. Unfortunately, many pathologic processes of muscle are chronic and unrelenting. Under such conditions, any regenerative activity fails to keep pace with the disease and the loss of muscle fibers becomes permanent. The bulk of the muscle is then replaced by fat and


Neurology_Adams

Neurology_Adams. unrelenting. Under such conditions, any regenerative activity fails to keep pace with the disease and the loss of muscle fibers becomes permanent. The bulk of the muscle is then replaced by fat and collagenous connective tissue, typical, for example, of the muscular dystrophies.


Neurology_Adams

Neurology_Adams. THE DEVELOPMENT AND AGING OF MUSCLE (SEE ALSO CHAP. 28)


Neurology_Adams

Neurology_Adams. The accepted view of the embryogenesis of muscle is that muscle fibers form by fusion of myoblasts soon after the latter differentiate from somatic mesodermal cells. Muscle connective tissue derives from the somatopleural mesoderm. After fusion of the myoblasts, a series of cellular events including the sequential activation of myogenic transcription factors leads to myofibril formation. The newly formed fibers are thin, centrally nucleated tubes (appropriately called myotubes) in which myofilaments begin to be produced from polyribosomes. As myofilaments become organized into myofibrils, the nuclei of the muscle fiber are displaced peripherally to a subsarcolemmal position. Once the nuclei assume a peripheral position, the myofiber is fully formed. The detailed mechanisms whereby myoblasts seek one another, the manner in which each of a series of fused nuclei contributes to the myotube, the formation of actin and myosin fibrils, Z-discs, and the differentiation of a small residue of


Neurology_Adams

Neurology_Adams. seek one another, the manner in which each of a series of fused nuclei contributes to the myotube, the formation of actin and myosin fibrils, Z-discs, and the differentiation of a small residue of satellite cells on the surface of the fibers are reviewed by Rubenstein and Kelly.


Neurology_Adams

Neurology_Adams. The mechanisms that determine the number and arrangement of fibers in each muscle are not as well understood. Presumably, the myoblasts themselves possess the genetic information that controls the program of development, but within any given species there are wide individual variations that account for obvious differences in the size of muscles and their power of contraction.


Neurology_Adams

Neurology_Adams. The number of fibers assigned to each muscle is probably attained by birth, and growth of muscle thereafter depends mainly on the enlargement of fibers. Although the nervous system and musculature develop independently, muscle fibers continue to grow after birth only when they are active and under the influence of nerve. Measurements of muscle fiber diameters from birth to old age show the growth curve ascending rapidly in the early postnatal years and less rapidly in adolescence, reaching a peak during the third decade. After puberty, growth of muscle is less in females than in males, and such differences are greater in the arm, shoulder, and pelvic muscles than in the leg; growth in ocular muscles is about equal in the 2 sexes. At all ages, disuse of muscle decreases fiber size by as much as 30 percent, and overuse increases the size by about the same amount (work hypertrophy). Normally, type 1 (oxidative enzyme-rich) fibers are slightly smaller than type 2 (phosphorylative


Neurology_Adams

Neurology_Adams. by as much as 30 percent, and overuse increases the size by about the same amount (work hypertrophy). Normally, type 1 (oxidative enzyme-rich) fibers are slightly smaller than type 2 (phosphorylative enzyme-rich) fibers; the numerical proportions of the 2 fiber types vary in different muscles in accordance with the natural functions of that muscle. The exercising of young animal muscle causes a hypertrophy of high-oxidative type 1 fibers and an increase in the proportion of low-oxidative type 2 fibers; aging muscle lacks this capacity; exercise produces only an increase in the proportion of type 2 fibers (Silbermann et al). No such data are available in humans, but clinical observation suggests that with aging, the capacity of muscle to respond to intense, sustained exercise is diminished.


Neurology_Adams

Neurology_Adams. During late adult life, the number of muscle fibers diminishes and variation in fiber size increases as mentioned in Chap. 28 on aging. The variations are of 2 types: group atrophy, in which clusters of 20 to 30 fibers are all reduced in diameter to about the same extent, and random single-fiber atrophy. Also, muscle cells, like other cells of postmitotic type, are subject to aging changes (lipofuscin accumulation, autophagic vacuolization, enzyme loss) and to death. Group atrophy, present to a slight degree in the gastrocnemii of almost all individuals older than 60 years, represents denervation effect from an aging-related loss of lumbar motor neurons and peripheral nerve fibers. Further comments regarding muscle and aging can be found in the work of Tomlinson and colleagues and in Chap. 28.


Neurology_Adams

Neurology_Adams. Denervation from spinal motor neuron or nerve disease at every age has roughly the same effect; namely, atrophy of muscle fibers (first in random distribution, then in groups) and later, degeneration. Muscle necrosis at all ages excites a regenerative response from sarcolemmal and satellite cells in any intact parts of the fibers. If this occurs repeatedly, the regenerative potential wanes, with ultimate death of the fiber leading to permanent depopulation of fibers with the expected muscle weakness. The number and diversity of diseases of striated muscle greatly exceed the number of symptoms and signs by which they express themselves clinically; thus, different diseases share certain common symptoms and syndromes. To avoid excessive repetition in the description of individual diseases, we discuss here, in one place, the broad clinical manifestations of muscle disease.


Neurology_Adams

Neurology_Adams. 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. 23, 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. 23, 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,


Neurology_Adams

Neurology_Adams. 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. On the other hand, a rare example of a physiologic muscle disorder that simulates lassitude is lifelong exercise intolerance, often accompanied by muscle cramps during exercise, which has been traced to mutations in the cytochrome b gene of the mitochondrial DNA (Andreu et al). The subject of fatigue as a physiologic phenomenon and as a clinical feature of many psychiatric and medical diseases,


Neurology_Adams

Neurology_Adams. to mutations in the cytochrome b gene of the mitochondrial DNA (Andreu et al). 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. 23.


Neurology_Adams

Neurology_Adams. Evaluation of Muscle Weakness and Paralysis


Neurology_Adams

Neurology_Adams. 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


Neurology_Adams

Neurology_Adams. 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 23.


Neurology_Adams

Neurology_Adams. 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


Neurology_Adams

Neurology_Adams. 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.


Neurology_Adams

Neurology_Adams. 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. As mentioned, one can distinguish true weakness from unwillingness to cooperate, feigned or neurasthenic weakness, and inhibition of movement by pain.


Neurology_Adams

Neurology_Adams. 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: 2—Active movement only with gravity eliminated 3—Full movement against gravity but cannot offer resistance to manual muscle opposition Further gradations may be added, specified as 4+ for barely detectable weakness and 4for easily detected weakness, 3+ and 3-, and so on.


Neurology_Adams

Neurology_Adams. Further gradations may be added, specified as 4+ for barely detectable weakness and 4for easily detected weakness, 3+ and 3-, and so on. 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. It is most convenient to compare power generated by 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 45-1. A practiced examiner can survey the strength of these muscle groups in 2 to 3 min.


Neurology_Adams

Neurology_Adams. 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., this textbook) 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


Neurology_Adams

Neurology_Adams. Changes in the Contractile Process These processes relate to qualitative changes in muscle contraction. 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 cause 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. 46.


Neurology_Adams

Neurology_Adams. 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 s), or at high rates of repetitive nerve stimulation (20 to 50 Hz), as described in Chap. 46.


Neurology_Adams

Neurology_Adams. 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 occur in the contracting or stretched muscles.


Neurology_Adams

Neurology_Adams. 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 (attached to Eulenburg’s name). 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 of muscle in Chap. 46. 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


Neurology_Adams

Neurology_Adams. 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).


Neurology_Adams

Neurology_Adams. 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 paramyotonia, 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. 46.


Neurology_Adams

Neurology_Adams. 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 other conditions, where phosphorylase seems to be present but nonfunctional. 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


Neurology_Adams

Neurology_Adams. 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.


Neurology_Adams

Neurology_Adams. 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 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


Neurology_Adams

Neurology_Adams. 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.


Neurology_Adams

Neurology_Adams. 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.


Neurology_Adams

Neurology_Adams. Notably, most primary muscle diseases are painless. 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


Neurology_Adams

Neurology_Adams. 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).


Neurology_Adams

Neurology_Adams. 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).


Neurology_Adams

Neurology_Adams. 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.


Neurology_Adams

Neurology_Adams. 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 one or a few 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.


Neurology_Adams

Neurology_Adams. 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 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, is described further on.


Neurology_Adams

Neurology_Adams. 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


Neurology_Adams

Neurology_Adams. 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, are discussed in Chap. 46.


Neurology_Adams

Neurology_Adams. 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.


Neurology_Adams

Neurology_Adams. 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.


Neurology_Adams

Neurology_Adams. Topographic 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. 43, 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.


Neurology_Adams

Neurology_Adams. 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. The rare primary disease of ocular muscle (progressive external ophthalmoplegia) is usually symmetric and does not produce diplopia. 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


Neurology_Adams

Neurology_Adams. (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.


Neurology_Adams

Neurology_Adams. 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. Ptosis has a wider diagnostic range than ophthalmoplegia that includes myotonic dystrophy. Although not a regular feature of the disease, ophthalmoparesis can occur in the Lambert-Eaton myasthenic syndrome.


Neurology_Adams

Neurology_Adams. Ptosis is variable in all of these conditions. When present in infantile myopathic disease, it is frequently a marker of the congenital myasthenic syndromes. The periorbital edema of Trichinosis is a rare cause, associated also with periorbital edema.


Neurology_Adams

Neurology_Adams. 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).


Neurology_Adams

Neurology_Adams. 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.


Neurology_Adams

Neurology_Adams. 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. 38); 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.


Neurology_Adams

Neurology_Adams. 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.


Neurology_Adams

Neurology_Adams. 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).


Neurology_Adams

Neurology_Adams. 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 spine syndrome (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.


Neurology_Adams

Neurology_Adams. 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 encode 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, “Central Core Myopathy (RYR1 Mutation).”


Neurology_Adams

Neurology_Adams. 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.


Neurology_Adams

Neurology_Adams. 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. 43). The diaphragm and accessory muscles may be severely affected


Neurology_Adams

Neurology_Adams. in the thorax by tumor or aortic aneurysm; an idiopathic or postinfectious variety may be related to brachial plexitis (see Chap. 43). 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.