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he spine and the proximal portion of nerves are the usual abnormal sites underlying flaccid weakness of one limb. Many conditions that cause paraplegia or quadriplegia begin as monoplegia. Therefore, one must also consult the differential diagnosis of spinal paraplegia provided in Table 12-1 when considering monoplegia. In addition, several cerebral disorders that cause hemiplegia may begin as a monoplegia, so tables in Chapter 11 are also applicable.
APPROACH TO MONOPLEGIA Either pain or weakness may cause refusal to use a limb. The cause of most painful limbs is injury. Other causes are arthritis, infection, and tumor. A trivial pull on an infant’s arm may dislocate the radial head and cause an apparent monoplegia. Pain and weakness together are a feature of plexitis. Table 13-1 summarizes the differential diagnosis of acute monoplegia. Plexopathies and neuropathies are the leading causes of pure monoplegia. Stroke often affects one limb more than the others, usually the arm more than the leg. The presentation may suggest monoplegia, but careful examination often reveals increased tendon reflexes and an extensor plantar response in the seemingly unaffected leg. Any suggestion of hemiplegia rather than monoplegia or increased tendon reflexes in the paretic limb should focus attention on the brain and cervical cord as the pathological sites. Chronic progressive brachial monoplegia is uncommon. When it occurs, one should suspect syringomyelia and tumors of the cervical cord or brachial plexus. Chronic progressive weakness of one leg suggests a tumor of the spinal cord or a neurofibroma of the lumbar plexus. A monomelic form of spinal muscular atrophy, affecting only one leg or one arm,
should be considered when progressive weakness is not accompanied by sensory loss.
SPINAL MUSCULAR ATROPHIES The first report of a monomelic form of spinal muscular atrophy was from Asia, but the condition is probably equally common among Europeans. The terms used to describe the entity are benign focal amyotrophy and monomelic amyotrophy. Although trauma and immobilization of the limb may precede the onset of atrophy by several months, a cause-and-effect relationship is not established. The transmission of the familial form is by autosomal recessive inheritance. Two affected brothers had a mutation in the superoxide dismutase 1 gene. In one set of male identical twins, both developed atrophy of first one hand and then the other.
Table 13-1
Differential Diagnosis of Acute Monoplegia
Complicated migraine (see Chapter 11) Dislocation of the radial head Hemiparetic seizures (see Chapter 11) Monomelic spinal muscular atrophy Plexopathy and neuropathy Acute neuritis Asthmatic plexitis Idiopathic plexitis Osteomyelitis plexitis Poliomyelitis (see Chapter 7) Tetanus toxoid plexitis Hereditary Hereditary brachial neuritis Hereditary neuropathy with liability to pressure palsy Injury Lacerations Pressure injuries Traction injuries Stroke (see Table 11-2)
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Clinical Features. Onset is usually in the second or third decade, and there is a male preponderance. The initial features are usually weakness and atrophy in one limb, the arm in 75% and the leg in 25%. Tendon reflexes in the involved limb are hypoactive or absent. Sensation is normal. The weakness and atrophy affect only one limb in half of cases and spread to the contralateral limb in the remainder. Tremor of one or both hands is often associated with the wasting. The appearance of fasciculations heralds weakness and wasting. Progression is slow, and spontaneous arrest within 5 years is the rule. However, another limb may become weak after a gap of 15 years. Diagnosis. Needle electromyography (EMG) studies of all limbs are essential to show the extent of involvement. Motor conduction is normal. Magnetic resonance imaging of the spine and plexus is required to exclude a tumor. Management. Physical therapy, occupational therapy, splinting, and bracing are the main treatment options.
PLEXOPATHIES Acute Idiopathic Plexitis Acute plexitis is a demyelinating disorder of the brachial or lumbar plexus thought to be immune mediated. Brachial plexitis is far more common than lumbar plexitis.
Brachial Plexitis Brachial plexitis (brachial neuritis, neuralgic amyotrophy) occurs from infancy to adult life. Previous tetanus toxoid immunization has occurred in 10% to 20% of childhood and adult cases and in almost all infant cases. The site of immunization does not correlate with the limb involved. Clinical Features. The onset of symptoms is usually explosive. Pain is the initial feature in 95% of patients. Pain localizes to the shoulder but may be more diffuse or limited to the lower arm. Pain is severe. It may awaken the patient and is described as sharp, stabbing, throbbing, or aching. The duration of pain, which is frequently constant, varies from several hours to 3 weeks. As the pain subsides, weakness appears. Weakness is in the distribution of the upper plexus alone in half of patients and the entire plexus in most of the rest. Lower plexitis
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alone is unusual. Although the initial pain abates, paresthesias may accompany the weakness. Two thirds of people report improved strength during the month after onset. Upper plexus palsies improve faster than do lower plexus palsies. Among all patients, one third recover within 1 year, three fourths by 2 years, and 90% by 3 years. After 3 years, further improvement may occur, but permanent residua are expected. Recurrences are unusual and less severe than the initial episode. Diagnosis. Pain and weakness in one arm are also symptoms of spinal cord compression, indicating the need for spinal cord imaging studies. However, when the onset is characteristic of brachial plexus neuritis, the clinical features alone establish the diagnosis. Diagnostic tests are not essential. The cerebrospinal fluid is usually normal. Slight lymphocytosis and a slight increase in protein content are sometimes noted. EMG and nerve conduction studies are helpful in showing the extent of plexopathy. Electrical evidence of bilateral involvement may be present in patients with unilateral symptoms. Management. Corticosteroids do not affect the outcome. Range-of-motion exercises are recommended until strength recovers.
Lumbar Plexitis Lumbar plexitis occurs at all ages and is similar to brachial plexitis, except that it affects the leg instead of the arm. The mechanism is probably the same as in brachial plexitis. Clinical Features. Fever is often the first symptom, followed by pain in one or both legs. The pain has an abrupt onset and may occur in a femoral or sciatic distribution. Sciatica, when present, suggests disk disease. Young children refuse to stand or walk, and older children limp. Weakness may develop concurrently with pain or be delayed for as long as 3 weeks. The onset of weakness is insidious and often difficult to date, but usually it begins 8 days after the onset of pain. Weakness progresses for a week and then stabilizes. Tendon reflexes are absent in the affected leg but are present in other limbs. Recovery is characterized first by abatement of pain and then by increasing strength. The average time from onset of pain to maximal recovery is 18 weeks, with a range of 8 weeks to several years. Functional recovery is almost universal, but mild weakness may persist.
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Diagnosis. The sudden onset of pain and weakness in one leg suggests spinal cord or disk disease. MRI of the spine is a means of excluding other disorders; the results are invariably normal in lumbar plexitis. The cerebrospinal fluid is normal except for a slight increase in the protein concentration. EMG performed 3 weeks after onset shows patchy denervation. Management. Corticosteroids do not affect the outcome. Range-of-motion exercises are necessary to ensure the best recovery.
Acute Symptomatic Plexitis Asthmatic Amyotrophy (Hopkins Syndrome) Sudden flaccid paralysis of one or more limbs, resembling poliomyelitis, may occur during recovery from an asthmatic attack. All affected children had previously received poliomyelitis vaccine. The probable cause of the syndrome is an infection by a neurotropic virus other than poliovirus. Adenovirus, echovirus, and coxsackievirus have been isolated from stool, throat, or cerebrospinal fluid in some cases. Clinical Features. Age at onset is from 1 to 11 years, and the male-to-female ratio is 7:4. The interval between the asthmatic attack and the paralysis is 1 to 11 days, with an average of 5 days. Monoplegia occurs in 90%, with the arm involved twice as often as the leg. The other 10% have hemiplegia or diplegia. Meningeal irritation is not present. Sensation is intact, but the paralyzed limb is painful in half of cases. Recovery is incomplete, and all affected children have some degree of permanent paralysis. Diagnosis. Asthmatic amyotrophy is primarily a clinical diagnosis based on the sequence of events. The diagnosis requires distinction from paralytic poliomyelitis and idiopathic brachial neuritis. The basis for excluding paralytic poliomyelitis is normal cerebrospinal fluid in asthmatic amyotrophy. A few white blood cells may be present in the cerebrospinal fluid but never to the extent encountered in poliomyelitis, and the protein concentration is normal. EMG during the acute phase shows active denervation of the paralyzed limb, but the pattern of denervation does not follow the radicular distribution expected in a brachial neuritis.
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Management. Treatment is symptomatic and includes analgesics for pain and physical therapy.
Hereditary Brachial Plexopathy The two major phenotypes of focal familial recurrent neuropathy are hereditary brachial plexopathy (also called hereditary neuralgic amyotrophy) and hereditary neuropathy with liability to pressure palsies (see “Mononeuropathies”). The phenotypes can be confused because isolated nerve palsies may occur in hereditary brachial plexopathy, and brachial plexopathy occurs in patients with hereditary neuropathy with a liability to pressure palsies. Transmission of both disorders is by autosomal dominant inheritance, but the underlying mutations are at different sites on chromosome 17. The location of the responsible gene for hereditary brachial plexopathy is chromosome 17q25 (Sto¨gbauer et al, 2000). Clinical Features. Hereditary brachial plexopathy may be difficult to distinguish from idiopathic brachial plexitis in the absence of a family or patient history of similar episodes. Events that may trigger an attack in genetically predisposed individuals include infection, emotional stress, strenuous use of the affected limb, and childbirth. Immunization, which may precipitate sporadic brachial plexopathies, is not a factor in the genetic form. Two different courses exist, but with only one type per family, suggesting the possibility of genetic heterogeneity (van Alfen et al, 2000). Characteristic of the classic course is severe attacks with relatively symptom-free intervals. Patients with the chronic course experience interictal persistence of pain and weakness. The initial attack usually occurs during the second or third decade but may appear at birth. Attributing palsies at birth to trauma is common despite the positive family history. Weakness resolves completely, only to recur later. Severe arm pain exacerbated by movement characterizes the attack. Weakness follows in days to weeks, which is usually maximal within a few days and always by 1 month. The entire plexus may be involved, but more often only the upper trunk is affected. Even with total plexus involvement, the upper plexus is weaker than other parts. Examination shows proximal arm weakness. Distal weakness may be present as well. Tendon reflexes are absent from affected muscles. Weakness persists for weeks to months and is associated with atrophy and
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fasciculations. Pain, which is frequently the only sensory finding, subsides after the first week. Recovery begins weeks to months after attaining maximal weakness. Return of function is usually complete, although some residual weakness may persist after repeated attacks. The frequency of attacks varies; several attacks may occur within a single year, but the usual pattern is two or three attacks per decade. Occasional children have an episode of lumbar plexopathy. Pain in the thigh and proximal weakness are characteristic. Brachial and lumbar plexopathies are never concurrent, although bilateral brachial plexopathy is a relatively common event. Isolated cranial nerve palsies may occur in families with hereditary brachial plexopathy. The vagus nerve is the one most often affected and causes hoarseness and dysphagia. Other cranial neuropathies result in transitory facial palsy and unilateral hearing loss. Diagnosis. The family history, early age at onset, unique triggering events, recurrences, and involvement of other nerves differentiate hereditary brachial plexopathy from idiopathic brachial neuritis. EMG shows a diffuse axonopathy in the affected arm and some evidence of denervation in the asymptomatic arm. Asymptomatic legs are electrically normal. Management. Analgesics are useful at the onset of an attack. Range-of-motion exercises prevent contractures. Corticosteroid use is not beneficial.
Neonatal Traumatic Brachial Neuropathy The incidence of neonatal brachial plexus birth injuries is estimated at 1 in 1000 live births. It seems likely that the incidence has increased in recent years because of the societal and financial pressures to avoid cesarean section. The cause of obstetrical brachial plexus palsies is excessive traction on the plexus. Upper plexus injuries occur when pulling the head and arm away from each other. This occurs in the vertex position when the head is pulling forcefully to deliver the aftercoming shoulder or when normal contractions force the head and neck downward with the shoulder trapped by the pelvis. Injuries in the breech position occur when pulling the arm downward to free the aftercoming head
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or when rotating the head to occipitoanterior when the shoulder is fixed. Complete (upper and lower) plexus injuries occur during vertex deliveries when traction is exerted on a prolapsed arm and in breech deliveries when the trunk is pulled downward but an aftercoming arm is fixed. Clinical Features. Most neonatal brachial plexus injuries occur in large full-term newborns of primiparous mothers, especially when the fetus is malpositioned and the delivery is long and difficult. The traditional division of brachial plexus injuries is into those involving the upper roots (named for Erb and Duchenne) and those involving the lower roots (named for Klumpke). However, solitary lower root injuries are unusual. In 88%, the palsy affects only the C5 through C7 cervical roots, and 12% have a complete plexus palsy. Bilateral, but not necessarily symmetrical, involvement occurs in 8% of cases. Because the upper plexus (C5–C7) is always involved, the posture of the arm is typical and reflects weakness of the proximal muscles. The arm is abducted and internally rotated at the shoulder and is extended and pronated at the elbow, so that the partially flexed fingers face backward. Extension of the wrist is lost and the fingers are fisted. The biceps and triceps reflexes are absent. Injuries that extend higher than the C4 segment result in ipsilateral diaphragmatic paralysis. Newborns with complete brachial plexus palsies have flaccid, dry limbs with neither proximal nor distal movement. Horner syndrome is sometimes associated. Sensory loss to pinprick is present with partial or complete palsies, but may not conform to the segmental pattern of weakness. Diagnosis. Recognition of brachial plexus palsy is through the typical posture of the arm and failure of movement when the Moro reflex is tested. Because the injury often takes place during a long and difficult delivery, asphyxia may be present as well. In such cases, generalized hypotonia may mask the focal arm weakness. Approximately 10% of newborns with brachial plexus injuries have facial nerve palsy and fractures of the clavicle or humerus. Management. The spontaneous recovery rate is approximately 70%. One goal of therapy is to prevent the development of contractures. Range-ofmotion exercises prevent contractures, whereas splinting, or other forms of immobilization, cause them. Significant recovery occurs throughout
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the first year, but infants who show no improvement in strength at the end of 6 months are unlikely to show functional improvement later. Surgical reconstruction of the plexus (e.g., nerve grafts, neuroma excision) is a consideration in infants with no evidence of spontaneous recovery at 6 months. However, the benefit of reconstructive surgery is not established.
Osteomyelitis-Neuritis Apparent limb weakness caused by pain is a well-recognized phenomenon. However, a true brachial neuritis may occur in response to osteomyelitis of the shoulder. Ischemic nerve damage caused by vasculitis is the presumed mechanism. Clinical Features. Osteomyelitis-neuritis occurs predominantly during infancy. The initial feature is a flaccid arm without pain or tenderness. Body temperature may be normal at first but soon increases. Pain develops on movement of the shoulder, and tenderness to palpation follows. No swelling is present. The biceps and triceps reflexes may be depressed or absent. Diagnosis. Suspect osteomyelitis of the proximal humerus when brachial plexitis develops during infancy. Radiographs of the humerus become abnormal at the end of the first week, when they show destruction of the lateral margin of the humerus, but a radioisotope bone scan shows a focal area of uptake in the proximal humerus, the scapula, or both shortly after onset. After 3 weeks, EMG shows patchy denervation in the muscles innervated by the upper plexus. These results support the idea that this is a true plexitis and not just a painful limb. Aspirates from the shoulder joint or blood culture identify the organism. Group B streptococcus is often isolated in specimens from young infants. Older children have other bacterial species. Management. A 3- to 4-week course of intravenous antibiotics, usually penicillin, is the recommended treatment. Recovery of arm strength may be incomplete.
Postnatal Injuries BRACHIAL PLEXUS
Traction and pressure injuries of the brachial plexus are relatively common because of its superficial position. Motor vehicle and sports accidents account for the majority of severe
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injuries. However, mild injuries also occur in the following situations: (1) when an adult suddenly yanks a child’s arm, either protectively or to force movement; (2) with a blow to the shoulder, such as in a football scrimmage or from the recoil of a rifle; (3) with prolonged wearing of a heavy backpack; (4) when the arm is kept hyperextended during surgery; and (5) with pressure in the axilla from poorly positioned crutches. Clinical Features. Mild injuries do not affect all portions of the plexus equally. Diffuse weakness is uncommon. Pain may be an important initial feature, and sensory loss is uncommon. Recovery begins within days or weeks and is complete. Atrophy does not occur. More severe injuries are usually associated with fractures of the clavicle and scapula and dislocation of the humerus. The upper plexus is generally affected more severely than is the lower plexus, but complete paralysis may be present at the onset. Sensory loss is less marked than weakness, and the two may not correspond in distribution. Pain is common, not only from the plexopathy but also from the bone and soft-tissue injuries. The most painful injuries are those associated with root avulsion. Tendon reflexes are absent, and atrophy develops in denervated muscle. Recovery progresses proximally to distally and the Tinel sign plots the recovery: tingling in the distal part of a limb caused by tapping over the regenerating segment of a nerve. Complete reinnervation, when it occurs, may take several months or years. The completeness of recovery depends on the severity and nature of the injury. Pressure and traction injuries in which anatomical integrity is not disturbed recover best, whereas injuries that tear the nerve or avulse the root do not recover at all. Diagnosis. EMG is useful in identifying the pattern of nerve injury and in providing information on the prognosis. Even with mild traction injuries, the amplitude of motor and sensory action potentials attenuates and motor and sensory conduction slows. Management. Mild injuries do not require treatment other than range-of-motion exercises. For more severe traction injuries, resting the limb for the first month is usually necessary. During that time, provide analgesia as needed for pain and electrically stimulate muscles away from the site of injury to maintain tone. Initiate range-of-motion exercises when pain subsides.
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Prompt correction is required of fractures and dislocations that cause pressure on the brachial plexus. Lacerated nerves require surgical restoration of anatomical integrity. LUMBAR PLEXUS
Injuries of the lumbar plexus are much less common than are injuries of the brachial plexus. The pelvis and the heavy muscles of the hip provide considerable protection from direct trauma. Clinical Features. Lumbar plexus injuries are usually associated with fracture-dislocation of the pelvis. Motor vehicle accidents or falls from a considerable height are required to produce sufficient force to fracture the pelvis. Therefore, the patient usually has multiple injuries, and the lumbar plexus injury may be the last one identified. Lumbar plexus injuries produce a patchy weakness that is difficult to differentiate from mononeuritis multiplex. Diagnosis. EMG helps distinguish plexus injuries and nerve injuries. Management. Fracture-dislocations require treatment to relieve pressure on the plexus. As with brachial plexus injuries, the completeness of recovery depends on the anatomical integrity of the nerves.
Plexus Tumors Plexus tumors in childhood are rare. The most common primary tumor is the plexiform neurofibroma (Fig. 13-1). These can affect either the brachial or lumbar plexus. They grow very slowly and cause progressive but selected weakness over several years. Secondary tumors of the brachial plexus are neuroblastomas and primitive neuroectodermal tumors arising in the chest. MRI is used to visualize plexus tumors when fat subtraction techniques are used.
Mononeuropathies Radial Neuropathy Radial nerve injuries usually occur in the spinal groove of the humerus, just below the takeoff of the motor branch to the triceps muscle. Injury may occur with fractures of the humerus or by external pressure. Such
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Figure 13-1 Neurofibroma of the lumbar plexus. Magnetic resonance imaging of the plexus using a subtraction technique shows enlargement of the sciatic nerve (arrow).
pressure usually results when a sleeping or sedated patient is in a position that compresses the nerve between the humerus and a hard surface, such as an operating table and chair. Isolated radial nerve injuries may occur in newborns with a history of failure of progression of labor. These may result from prolonged radial nerve compression (Hayman et al, 1999). Clinical Features. Wristdrop and fingerdrop are characteristic of injuries to the radial nerve within the spiral groove. The brachioradialis muscle may be weak and its tendon reflex lost. Sensory disturbances are restricted to the back of the hand near the base of the thumb. With the wrist dropped, a fist is mechanically difficult to make, but the finger flexors are not weak. Diagnosis. Electrophysiological studies are useful for locating the site of injury and assessing the anatomical integrity of the nerve and the prognosis for recovery. Management. Pressure injuries recover completely in 6 to 8 weeks. During that time, a splint is useful for placing the wrist in extension so that the patient can flex his or her fingers.
Ulnar Neuropathy The most common site of ulnar injury is the elbow. This injury may result from external
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pressure, recurrent dislocation of the nerve from its groove, or fracture of the distal humerus. Clinical Features. Paresthesias on the ulnar side of the hand, the little finger, and the ring finger are experienced. Tapping the ulnar groove increases the discomfort. Hand strength is lost, and the intrinsic muscles become wasted. The little finger and the adjacent side of the ring finger have diminished or absent sensation. Diagnosis. Electrophysiological techniques localize the injury along the course of the nerve. Management. Minor pressure injuries do not require treatment, and recovery is complete within a few weeks. Injuries to the elbow that cause fracture or nerve dislocation require surgical repair.
Median Neuropathy The cause of nontraumatic median neuropathies is compression of the nerve in the carpal tunnel and traumatic injuries at the elbow. In children, a storage disease such as mucolipidosis may cause nerve compression in the carpal tunnel, but idiopathic cases occur as well. Fracture at the elbow is the usual cause of traumatic median neuropathy. Clinical Features. The most common features are numbness and pain in the hand. Nontraumatic median neuropathy is often bilateral. Weakness and atrophy are more likely to occur in traumatic injuries of the nerve than in carpal tunnel entrapment. Diagnosis. EMG is useful to localize the lesion, especially when surgical decompression is an option. Management. Surgical decompression may be beneficial for both nontraumatic and traumatic injuries.
Peroneal Neuropathy The peroneal nerve lies in a superficial position adjacent to the fibula. External pressure readily compresses the nerve against the bone. This most often occurs in children who have undergone significant weight loss or trauma to the nerve. EMG documented a prenatal peroneal palsy, presumably caused by pressure in a newborn (Jones et al, 1996).
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Clinical Features. The prominent feature is an acute, painless footdrop. Both dorsiflexion and eversion of the foot are weak. Sensation is usually intact, but sometimes there is numbness over the lower lateral leg and dorsum of the foot. When only the deep branch of the peroneal nerve is involved, sensory loss is restricted to a small triangle between the first two toes. Complete or significant spontaneous recovery is the rule except after considerable trauma. Diagnosis. Electrodiagnosis is useful to discriminate peroneal nerve lesions from disturbances of the fifth lumbar root. Management. A footdrop brace is a useful walking aid until recovery is complete.
Hereditary Neuropathy with Liability to Pressure Palsy The characteristic feature of hereditary neuropathy with liability to pressure palsy (also called tomaculous neuropathy) is the development of a mononeuropathy after a minor trauma. In some cases, the brachial plexus is affected. Transmission of the disorder is as an autosomal dominant trait caused by deletion of the gene encoding peripheral myelin protein-22 caused by a deletion in chromosome 17p11.2 (Bird, 2008). Clinical Features. The first episode usually occurs during the second or third decade. Typical precipitating factors include sleeping on a limb, body contact in sports, constrictive clothing, or positioning during surgery. Individuals quickly learn to avoid activities that provoke episodes. Superficial nerves (radial, ulnar, median, peroneal) are the ones most commonly affected. The resulting mononeuropathy is painless and affects both motor and sensory fibers. Tendon reflexes are lost. Recovery is complete within days to weeks. Diagnosis. Except for the family history, the first episode might suggest ordinary pressure palsy, although the trivial nature of the trauma should alert the physician to the underlying neuropathy. Consider the diagnosis in children with repeated neuropathies or multifocal neuropathies even in the absence of a family history. Molecular genetic testing establishes the diagnosis. Electrophysiological studies show slow conduction time, not only in the affected
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limb but also in all limbs. Other family members may show generalized slowing of conduction between attacks. Management. No treatment is available for the underlying neuropathy. Alterations in lifestyle may be needed to avoid pressure palsies. A wrist splint is useful for carpal tunnel syndrome and an ankle-foot orthosis for footdrop. Protective pads at elbows or knees may prevent pressure and trauma to local nerves. Advise patients against sitting with legs crossed, leaning on elbows, and activities requiring repetitive movements. Despite the best effort, some patients eventually develop a generalized motor and sensory neuropathy.
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REFERENCES Bird T: Hereditary neuropathy with liability to pressure palsy. In GeneClinics: Medical Genetics Knowledge Base [online database]. Seattle, University of Washington, January 14, 2008. Available at: http://www.geneclinic.org. Hayman M, Roland EH, Hill A: Newborn radial nerve palsy: report of four cases and review of published reports, Pediatr Neurol 21:648–651, 1999. Jones HR Jr, Herbison GJ, Jacobs SR, et al: Intrauterine onset of a mononeuropathy: peroneal neuropathy in a newborn with electromyographic findings at age one day compatible with prenatal onset, Muscle Nerve 19:88–91, 1996. Sto¨gbauer F, Young P, Kuhlenbaumer G, et al: Hereditary recurrent focal neuropathies: clinical and molecular features, Neurology 54:546–551, 2000. van Alfen N, van Engelen BGM, Reinders JWC, et al: The natural history of hereditary neuralgic amyotrophy in the Dutch population: two distinct types? Brain 123: 718–723, 2000.
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he spine and the proximal portion of nerves are the usual abnormal sites underlying flaccid weakness of one limb. Many conditions that cause paraplegia or quadriplegia begin as monoplegia. Therefore, one must also consult the differential diagnosis of spinal paraplegia provided in Table 12-1 when considering monoplegia. In addition, several cerebral disorders that cause hemiplegia may begin as a monoplegia, so tables in Chapter 11 are also applicable.
APPROACH TO MONOPLEGIA Either pain or weakness may cause refusal to use a limb. The cause of most painful limbs is injury. Other causes are arthritis, infection, and tumor. A trivial pull on an infant’s arm may dislocate the radial head and cause an apparent monoplegia. Pain and weakness together are a feature of plexitis. Table 13-1 summarizes the differential diagnosis of acute monoplegia. Plexopathies and neuropathies are the leading causes of pure monoplegia. Stroke often affects one limb more than the others, usually the arm more than the leg. The presentation may suggest monoplegia, but careful examination often reveals increased tendon reflexes and an extensor plantar response in the seemingly unaffected leg. Any suggestion of hemiplegia rather than monoplegia or increased tendon reflexes in the paretic limb should focus attention on the brain and cervical cord as the pathological sites. Chronic progressive brachial monoplegia is uncommon. When it occurs, one should suspect syringomyelia and tumors of the cervical cord or brachial plexus. Chronic progressive weakness of one leg suggests a tumor of the spinal cord or a neurofibroma of the lumbar plexus. A monomelic form of spinal muscular atrophy, affecting only one leg or one arm,
should be considered when progressive weakness is not accompanied by sensory loss.
SPINAL MUSCULAR ATROPHIES The first report of a monomelic form of spinal muscular atrophy was from Asia, but the condition is probably equally common among Europeans. The terms used to describe the entity are benign focal amyotrophy and monomelic amyotrophy. Although trauma and immobilization of the limb may precede the onset of atrophy by several months, a cause-and-effect relationship is not established. The transmission of the familial form is by autosomal recessive inheritance. Two affected brothers had a mutation in the superoxide dismutase 1 gene. In one set of male identical twins, both developed atrophy of first one hand and then the other.
Table 13-1
Differential Diagnosis of Acute Monoplegia
Complicated migraine (see Chapter 11) Dislocation of the radial head Hemiparetic seizures (see Chapter 11) Monomelic spinal muscular atrophy Plexopathy and neuropathy Acute neuritis Asthmatic plexitis Idiopathic plexitis Osteomyelitis plexitis Poliomyelitis (see Chapter 7) Tetanus toxoid plexitis Hereditary Hereditary brachial neuritis Hereditary neuropathy with liability to pressure palsy Injury Lacerations Pressure injuries Traction injuries Stroke (see Table 11-2)
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Clinical Features. Onset is usually in the second or third decade, and there is a male preponderance. The initial features are usually weakness and atrophy in one limb, the arm in 75% and the leg in 25%. Tendon reflexes in the involved limb are hypoactive or absent. Sensation is normal. The weakness and atrophy affect only one limb in half of cases and spread to the contralateral limb in the remainder. Tremor of one or both hands is often associated with the wasting. The appearance of fasciculations heralds weakness and wasting. Progression is slow, and spontaneous arrest within 5 years is the rule. However, another limb may become weak after a gap of 15 years. Diagnosis. Needle electromyography (EMG) studies of all limbs are essential to show the extent of involvement. Motor conduction is normal. Magnetic resonance imaging of the spine and plexus is required to exclude a tumor. Management. Physical therapy, occupational therapy, splinting, and bracing are the main treatment options.
PLEXOPATHIES Acute Idiopathic Plexitis Acute plexitis is a demyelinating disorder of the brachial or lumbar plexus thought to be immune mediated. Brachial plexitis is far more common than lumbar plexitis.
Brachial Plexitis Brachial plexitis (brachial neuritis, neuralgic amyotrophy) occurs from infancy to adult life. Previous tetanus toxoid immunization has occurred in 10% to 20% of childhood and adult cases and in almost all infant cases. The site of immunization does not correlate with the limb involved. Clinical Features. The onset of symptoms is usually explosive. Pain is the initial feature in 95% of patients. Pain localizes to the shoulder but may be more diffuse or limited to the lower arm. Pain is severe. It may awaken the patient and is described as sharp, stabbing, throbbing, or aching. The duration of pain, which is frequently constant, varies from several hours to 3 weeks. As the pain subsides, weakness appears. Weakness is in the distribution of the upper plexus alone in half of patients and the entire plexus in most of the rest. Lower plexitis
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alone is unusual. Although the initial pain abates, paresthesias may accompany the weakness. Two thirds of people report improved strength during the month after onset. Upper plexus palsies improve faster than do lower plexus palsies. Among all patients, one third recover within 1 year, three fourths by 2 years, and 90% by 3 years. After 3 years, further improvement may occur, but permanent residua are expected. Recurrences are unusual and less severe than the initial episode. Diagnosis. Pain and weakness in one arm are also symptoms of spinal cord compression, indicating the need for spinal cord imaging studies. However, when the onset is characteristic of brachial plexus neuritis, the clinical features alone establish the diagnosis. Diagnostic tests are not essential. The cerebrospinal fluid is usually normal. Slight lymphocytosis and a slight increase in protein content are sometimes noted. EMG and nerve conduction studies are helpful in showing the extent of plexopathy. Electrical evidence of bilateral involvement may be present in patients with unilateral symptoms. Management. Corticosteroids do not affect the outcome. Range-of-motion exercises are recommended until strength recovers.
Lumbar Plexitis Lumbar plexitis occurs at all ages and is similar to brachial plexitis, except that it affects the leg instead of the arm. The mechanism is probably the same as in brachial plexitis. Clinical Features. Fever is often the first symptom, followed by pain in one or both legs. The pain has an abrupt onset and may occur in a femoral or sciatic distribution. Sciatica, when present, suggests disk disease. Young children refuse to stand or walk, and older children limp. Weakness may develop concurrently with pain or be delayed for as long as 3 weeks. The onset of weakness is insidious and often difficult to date, but usually it begins 8 days after the onset of pain. Weakness progresses for a week and then stabilizes. Tendon reflexes are absent in the affected leg but are present in other limbs. Recovery is characterized first by abatement of pain and then by increasing strength. The average time from onset of pain to maximal recovery is 18 weeks, with a range of 8 weeks to several years. Functional recovery is almost universal, but mild weakness may persist.
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Diagnosis. The sudden onset of pain and weakness in one leg suggests spinal cord or disk disease. MRI of the spine is a means of excluding other disorders; the results are invariably normal in lumbar plexitis. The cerebrospinal fluid is normal except for a slight increase in the protein concentration. EMG performed 3 weeks after onset shows patchy denervation. Management. Corticosteroids do not affect the outcome. Range-of-motion exercises are necessary to ensure the best recovery.
Acute Symptomatic Plexitis Asthmatic Amyotrophy (Hopkins Syndrome) Sudden flaccid paralysis of one or more limbs, resembling poliomyelitis, may occur during recovery from an asthmatic attack. All affected children had previously received poliomyelitis vaccine. The probable cause of the syndrome is an infection by a neurotropic virus other than poliovirus. Adenovirus, echovirus, and coxsackievirus have been isolated from stool, throat, or cerebrospinal fluid in some cases. Clinical Features. Age at onset is from 1 to 11 years, and the male-to-female ratio is 7:4. The interval between the asthmatic attack and the paralysis is 1 to 11 days, with an average of 5 days. Monoplegia occurs in 90%, with the arm involved twice as often as the leg. The other 10% have hemiplegia or diplegia. Meningeal irritation is not present. Sensation is intact, but the paralyzed limb is painful in half of cases. Recovery is incomplete, and all affected children have some degree of permanent paralysis. Diagnosis. Asthmatic amyotrophy is primarily a clinical diagnosis based on the sequence of events. The diagnosis requires distinction from paralytic poliomyelitis and idiopathic brachial neuritis. The basis for excluding paralytic poliomyelitis is normal cerebrospinal fluid in asthmatic amyotrophy. A few white blood cells may be present in the cerebrospinal fluid but never to the extent encountered in poliomyelitis, and the protein concentration is normal. EMG during the acute phase shows active denervation of the paralyzed limb, but the pattern of denervation does not follow the radicular distribution expected in a brachial neuritis.
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Management. Treatment is symptomatic and includes analgesics for pain and physical therapy.
Hereditary Brachial Plexopathy The two major phenotypes of focal familial recurrent neuropathy are hereditary brachial plexopathy (also called hereditary neuralgic amyotrophy) and hereditary neuropathy with liability to pressure palsies (see “Mononeuropathies”). The phenotypes can be confused because isolated nerve palsies may occur in hereditary brachial plexopathy, and brachial plexopathy occurs in patients with hereditary neuropathy with a liability to pressure palsies. Transmission of both disorders is by autosomal dominant inheritance, but the underlying mutations are at different sites on chromosome 17. The location of the responsible gene for hereditary brachial plexopathy is chromosome 17q25 (Sto¨gbauer et al, 2000). Clinical Features. Hereditary brachial plexopathy may be difficult to distinguish from idiopathic brachial plexitis in the absence of a family or patient history of similar episodes. Events that may trigger an attack in genetically predisposed individuals include infection, emotional stress, strenuous use of the affected limb, and childbirth. Immunization, which may precipitate sporadic brachial plexopathies, is not a factor in the genetic form. Two different courses exist, but with only one type per family, suggesting the possibility of genetic heterogeneity (van Alfen et al, 2000). Characteristic of the classic course is severe attacks with relatively symptom-free intervals. Patients with the chronic course experience interictal persistence of pain and weakness. The initial attack usually occurs during the second or third decade but may appear at birth. Attributing palsies at birth to trauma is common despite the positive family history. Weakness resolves completely, only to recur later. Severe arm pain exacerbated by movement characterizes the attack. Weakness follows in days to weeks, which is usually maximal within a few days and always by 1 month. The entire plexus may be involved, but more often only the upper trunk is affected. Even with total plexus involvement, the upper plexus is weaker than other parts. Examination shows proximal arm weakness. Distal weakness may be present as well. Tendon reflexes are absent from affected muscles. Weakness persists for weeks to months and is associated with atrophy and
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fasciculations. Pain, which is frequently the only sensory finding, subsides after the first week. Recovery begins weeks to months after attaining maximal weakness. Return of function is usually complete, although some residual weakness may persist after repeated attacks. The frequency of attacks varies; several attacks may occur within a single year, but the usual pattern is two or three attacks per decade. Occasional children have an episode of lumbar plexopathy. Pain in the thigh and proximal weakness are characteristic. Brachial and lumbar plexopathies are never concurrent, although bilateral brachial plexopathy is a relatively common event. Isolated cranial nerve palsies may occur in families with hereditary brachial plexopathy. The vagus nerve is the one most often affected and causes hoarseness and dysphagia. Other cranial neuropathies result in transitory facial palsy and unilateral hearing loss. Diagnosis. The family history, early age at onset, unique triggering events, recurrences, and involvement of other nerves differentiate hereditary brachial plexopathy from idiopathic brachial neuritis. EMG shows a diffuse axonopathy in the affected arm and some evidence of denervation in the asymptomatic arm. Asymptomatic legs are electrically normal. Management. Analgesics are useful at the onset of an attack. Range-of-motion exercises prevent contractures. Corticosteroid use is not beneficial.
Neonatal Traumatic Brachial Neuropathy The incidence of neonatal brachial plexus birth injuries is estimated at 1 in 1000 live births. It seems likely that the incidence has increased in recent years because of the societal and financial pressures to avoid cesarean section. The cause of obstetrical brachial plexus palsies is excessive traction on the plexus. Upper plexus injuries occur when pulling the head and arm away from each other. This occurs in the vertex position when the head is pulling forcefully to deliver the aftercoming shoulder or when normal contractions force the head and neck downward with the shoulder trapped by the pelvis. Injuries in the breech position occur when pulling the arm downward to free the aftercoming head
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or when rotating the head to occipitoanterior when the shoulder is fixed. Complete (upper and lower) plexus injuries occur during vertex deliveries when traction is exerted on a prolapsed arm and in breech deliveries when the trunk is pulled downward but an aftercoming arm is fixed. Clinical Features. Most neonatal brachial plexus injuries occur in large full-term newborns of primiparous mothers, especially when the fetus is malpositioned and the delivery is long and difficult. The traditional division of brachial plexus injuries is into those involving the upper roots (named for Erb and Duchenne) and those involving the lower roots (named for Klumpke). However, solitary lower root injuries are unusual. In 88%, the palsy affects only the C5 through C7 cervical roots, and 12% have a complete plexus palsy. Bilateral, but not necessarily symmetrical, involvement occurs in 8% of cases. Because the upper plexus (C5–C7) is always involved, the posture of the arm is typical and reflects weakness of the proximal muscles. The arm is abducted and internally rotated at the shoulder and is extended and pronated at the elbow, so that the partially flexed fingers face backward. Extension of the wrist is lost and the fingers are fisted. The biceps and triceps reflexes are absent. Injuries that extend higher than the C4 segment result in ipsilateral diaphragmatic paralysis. Newborns with complete brachial plexus palsies have flaccid, dry limbs with neither proximal nor distal movement. Horner syndrome is sometimes associated. Sensory loss to pinprick is present with partial or complete palsies, but may not conform to the segmental pattern of weakness. Diagnosis. Recognition of brachial plexus palsy is through the typical posture of the arm and failure of movement when the Moro reflex is tested. Because the injury often takes place during a long and difficult delivery, asphyxia may be present as well. In such cases, generalized hypotonia may mask the focal arm weakness. Approximately 10% of newborns with brachial plexus injuries have facial nerve palsy and fractures of the clavicle or humerus. Management. The spontaneous recovery rate is approximately 70%. One goal of therapy is to prevent the development of contractures. Range-ofmotion exercises prevent contractures, whereas splinting, or other forms of immobilization, cause them. Significant recovery occurs throughout
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the first year, but infants who show no improvement in strength at the end of 6 months are unlikely to show functional improvement later. Surgical reconstruction of the plexus (e.g., nerve grafts, neuroma excision) is a consideration in infants with no evidence of spontaneous recovery at 6 months. However, the benefit of reconstructive surgery is not established.
Osteomyelitis-Neuritis Apparent limb weakness caused by pain is a well-recognized phenomenon. However, a true brachial neuritis may occur in response to osteomyelitis of the shoulder. Ischemic nerve damage caused by vasculitis is the presumed mechanism. Clinical Features. Osteomyelitis-neuritis occurs predominantly during infancy. The initial feature is a flaccid arm without pain or tenderness. Body temperature may be normal at first but soon increases. Pain develops on movement of the shoulder, and tenderness to palpation follows. No swelling is present. The biceps and triceps reflexes may be depressed or absent. Diagnosis. Suspect osteomyelitis of the proximal humerus when brachial plexitis develops during infancy. Radiographs of the humerus become abnormal at the end of the first week, when they show destruction of the lateral margin of the humerus, but a radioisotope bone scan shows a focal area of uptake in the proximal humerus, the scapula, or both shortly after onset. After 3 weeks, EMG shows patchy denervation in the muscles innervated by the upper plexus. These results support the idea that this is a true plexitis and not just a painful limb. Aspirates from the shoulder joint or blood culture identify the organism. Group B streptococcus is often isolated in specimens from young infants. Older children have other bacterial species. Management. A 3- to 4-week course of intravenous antibiotics, usually penicillin, is the recommended treatment. Recovery of arm strength may be incomplete.
Postnatal Injuries BRACHIAL PLEXUS
Traction and pressure injuries of the brachial plexus are relatively common because of its superficial position. Motor vehicle and sports accidents account for the majority of severe
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injuries. However, mild injuries also occur in the following situations: (1) when an adult suddenly yanks a child’s arm, either protectively or to force movement; (2) with a blow to the shoulder, such as in a football scrimmage or from the recoil of a rifle; (3) with prolonged wearing of a heavy backpack; (4) when the arm is kept hyperextended during surgery; and (5) with pressure in the axilla from poorly positioned crutches. Clinical Features. Mild injuries do not affect all portions of the plexus equally. Diffuse weakness is uncommon. Pain may be an important initial feature, and sensory loss is uncommon. Recovery begins within days or weeks and is complete. Atrophy does not occur. More severe injuries are usually associated with fractures of the clavicle and scapula and dislocation of the humerus. The upper plexus is generally affected more severely than is the lower plexus, but complete paralysis may be present at the onset. Sensory loss is less marked than weakness, and the two may not correspond in distribution. Pain is common, not only from the plexopathy but also from the bone and soft-tissue injuries. The most painful injuries are those associated with root avulsion. Tendon reflexes are absent, and atrophy develops in denervated muscle. Recovery progresses proximally to distally and the Tinel sign plots the recovery: tingling in the distal part of a limb caused by tapping over the regenerating segment of a nerve. Complete reinnervation, when it occurs, may take several months or years. The completeness of recovery depends on the severity and nature of the injury. Pressure and traction injuries in which anatomical integrity is not disturbed recover best, whereas injuries that tear the nerve or avulse the root do not recover at all. Diagnosis. EMG is useful in identifying the pattern of nerve injury and in providing information on the prognosis. Even with mild traction injuries, the amplitude of motor and sensory action potentials attenuates and motor and sensory conduction slows. Management. Mild injuries do not require treatment other than range-of-motion exercises. For more severe traction injuries, resting the limb for the first month is usually necessary. During that time, provide analgesia as needed for pain and electrically stimulate muscles away from the site of injury to maintain tone. Initiate range-of-motion exercises when pain subsides.
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Prompt correction is required of fractures and dislocations that cause pressure on the brachial plexus. Lacerated nerves require surgical restoration of anatomical integrity. LUMBAR PLEXUS
Injuries of the lumbar plexus are much less common than are injuries of the brachial plexus. The pelvis and the heavy muscles of the hip provide considerable protection from direct trauma. Clinical Features. Lumbar plexus injuries are usually associated with fracture-dislocation of the pelvis. Motor vehicle accidents or falls from a considerable height are required to produce sufficient force to fracture the pelvis. Therefore, the patient usually has multiple injuries, and the lumbar plexus injury may be the last one identified. Lumbar plexus injuries produce a patchy weakness that is difficult to differentiate from mononeuritis multiplex. Diagnosis. EMG helps distinguish plexus injuries and nerve injuries. Management. Fracture-dislocations require treatment to relieve pressure on the plexus. As with brachial plexus injuries, the completeness of recovery depends on the anatomical integrity of the nerves.
Plexus Tumors Plexus tumors in childhood are rare. The most common primary tumor is the plexiform neurofibroma (Fig. 13-1). These can affect either the brachial or lumbar plexus. They grow very slowly and cause progressive but selected weakness over several years. Secondary tumors of the brachial plexus are neuroblastomas and primitive neuroectodermal tumors arising in the chest. MRI is used to visualize plexus tumors when fat subtraction techniques are used.
Mononeuropathies Radial Neuropathy Radial nerve injuries usually occur in the spinal groove of the humerus, just below the takeoff of the motor branch to the triceps muscle. Injury may occur with fractures of the humerus or by external pressure. Such
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Figure 13-1 Neurofibroma of the lumbar plexus. Magnetic resonance imaging of the plexus using a subtraction technique shows enlargement of the sciatic nerve (arrow).
pressure usually results when a sleeping or sedated patient is in a position that compresses the nerve between the humerus and a hard surface, such as an operating table and chair. Isolated radial nerve injuries may occur in newborns with a history of failure of progression of labor. These may result from prolonged radial nerve compression (Hayman et al, 1999). Clinical Features. Wristdrop and fingerdrop are characteristic of injuries to the radial nerve within the spiral groove. The brachioradialis muscle may be weak and its tendon reflex lost. Sensory disturbances are restricted to the back of the hand near the base of the thumb. With the wrist dropped, a fist is mechanically difficult to make, but the finger flexors are not weak. Diagnosis. Electrophysiological studies are useful for locating the site of injury and assessing the anatomical integrity of the nerve and the prognosis for recovery. Management. Pressure injuries recover completely in 6 to 8 weeks. During that time, a splint is useful for placing the wrist in extension so that the patient can flex his or her fingers.
Ulnar Neuropathy The most common site of ulnar injury is the elbow. This injury may result from external
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pressure, recurrent dislocation of the nerve from its groove, or fracture of the distal humerus. Clinical Features. Paresthesias on the ulnar side of the hand, the little finger, and the ring finger are experienced. Tapping the ulnar groove increases the discomfort. Hand strength is lost, and the intrinsic muscles become wasted. The little finger and the adjacent side of the ring finger have diminished or absent sensation. Diagnosis. Electrophysiological techniques localize the injury along the course of the nerve. Management. Minor pressure injuries do not require treatment, and recovery is complete within a few weeks. Injuries to the elbow that cause fracture or nerve dislocation require surgical repair.
Median Neuropathy The cause of nontraumatic median neuropathies is compression of the nerve in the carpal tunnel and traumatic injuries at the elbow. In children, a storage disease such as mucolipidosis may cause nerve compression in the carpal tunnel, but idiopathic cases occur as well. Fracture at the elbow is the usual cause of traumatic median neuropathy. Clinical Features. The most common features are numbness and pain in the hand. Nontraumatic median neuropathy is often bilateral. Weakness and atrophy are more likely to occur in traumatic injuries of the nerve than in carpal tunnel entrapment. Diagnosis. EMG is useful to localize the lesion, especially when surgical decompression is an option. Management. Surgical decompression may be beneficial for both nontraumatic and traumatic injuries.
Peroneal Neuropathy The peroneal nerve lies in a superficial position adjacent to the fibula. External pressure readily compresses the nerve against the bone. This most often occurs in children who have undergone significant weight loss or trauma to the nerve. EMG documented a prenatal peroneal palsy, presumably caused by pressure in a newborn (Jones et al, 1996).
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Clinical Features. The prominent feature is an acute, painless footdrop. Both dorsiflexion and eversion of the foot are weak. Sensation is usually intact, but sometimes there is numbness over the lower lateral leg and dorsum of the foot. When only the deep branch of the peroneal nerve is involved, sensory loss is restricted to a small triangle between the first two toes. Complete or significant spontaneous recovery is the rule except after considerable trauma. Diagnosis. Electrodiagnosis is useful to discriminate peroneal nerve lesions from disturbances of the fifth lumbar root. Management. A footdrop brace is a useful walking aid until recovery is complete.
Hereditary Neuropathy with Liability to Pressure Palsy The characteristic feature of hereditary neuropathy with liability to pressure palsy (also called tomaculous neuropathy) is the development of a mononeuropathy after a minor trauma. In some cases, the brachial plexus is affected. Transmission of the disorder is as an autosomal dominant trait caused by deletion of the gene encoding peripheral myelin protein-22 caused by a deletion in chromosome 17p11.2 (Bird, 2008). Clinical Features. The first episode usually occurs during the second or third decade. Typical precipitating factors include sleeping on a limb, body contact in sports, constrictive clothing, or positioning during surgery. Individuals quickly learn to avoid activities that provoke episodes. Superficial nerves (radial, ulnar, median, peroneal) are the ones most commonly affected. The resulting mononeuropathy is painless and affects both motor and sensory fibers. Tendon reflexes are lost. Recovery is complete within days to weeks. Diagnosis. Except for the family history, the first episode might suggest ordinary pressure palsy, although the trivial nature of the trauma should alert the physician to the underlying neuropathy. Consider the diagnosis in children with repeated neuropathies or multifocal neuropathies even in the absence of a family history. Molecular genetic testing establishes the diagnosis. Electrophysiological studies show slow conduction time, not only in the affected
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limb but also in all limbs. Other family members may show generalized slowing of conduction between attacks. Management. No treatment is available for the underlying neuropathy. Alterations in lifestyle may be needed to avoid pressure palsies. A wrist splint is useful for carpal tunnel syndrome and an ankle-foot orthosis for footdrop. Protective pads at elbows or knees may prevent pressure and trauma to local nerves. Advise patients against sitting with legs crossed, leaning on elbows, and activities requiring repetitive movements. Despite the best effort, some patients eventually develop a generalized motor and sensory neuropathy.
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REFERENCES Bird T: Hereditary neuropathy with liability to pressure palsy. In GeneClinics: Medical Genetics Knowledge Base [online database]. Seattle, University of Washington, January 14, 2008. Available at: http://www.geneclinic.org. Hayman M, Roland EH, Hill A: Newborn radial nerve palsy: report of four cases and review of published reports, Pediatr Neurol 21:648–651, 1999. Jones HR Jr, Herbison GJ, Jacobs SR, et al: Intrauterine onset of a mononeuropathy: peroneal neuropathy in a newborn with electromyographic findings at age one day compatible with prenatal onset, Muscle Nerve 19:88–91, 1996. Sto¨gbauer F, Young P, Kuhlenbaumer G, et al: Hereditary recurrent focal neuropathies: clinical and molecular features, Neurology 54:546–551, 2000. van Alfen N, van Engelen BGM, Reinders JWC, et al: The natural history of hereditary neuralgic amyotrophy in the Dutch population: two distinct types? Brain 123: 718–723, 2000.