Transverse Myelitis and Neuralgic Amyotrophy - Springer · Transverse Myelitis and Neuralgic...

Transverse Myelitis and Neuralgic Amyotrophy

Allan Belzberga*, Glendaliz Bosquesb and Kelly Phamc

aDepartment of Neurosurgery, The Johns Hopkins Hospital, Baltimore, MD, USAbChildren’s Memorial Hermann Hospital, The University of Texas Health Science Center at Houston (UTHealth)Medical School, Houston, TX, USAcJohns Hopkins University, Baltimore, MD, USA

Abstract

Neuralgic amyotrophy (NA), a lower motor neuron (LMN) lesion, presents a flaccid monoplegia ofthe upper extremity in children. Transverse myelitis (TM) may present with either an LMN or anupper motor neuron (UMN) injury, depending on areas affected on the cord. Both entities areinflammatory and autoimmune in nature. Diagnosis is with MRI and serological studies as well asnerve conduction studies (NCS) and electromyography (EMG). Treatment varies slightly, butincludes immunosuppression with steroids, replacement of antibodies with plasmapheresis inaddition to intravenous immunoglobulin (IVIG), immunosuppressant, and antineoplastic agents.Further management includes rehabilitation measures with stretching, strengthening, range ofmotion, neuromuscular electrical stimulation, patient and family education, and equipment evalu-ation. Children with persistent LMN deficits and limited recovery (6–8 months after onset ofdisease) may warrant surgical considerations for peripheral nerve surgery. This may include theuse of nerve transfers. Secondary surgery, including muscle and tendon transfers, can be considered1–2 years after disease onset, if persistent residual deficits are present. Most children with NA havegood outcomes with resolution of symptoms and improvement in function. Children with TM havea less favorable outcome with one third resolution rate.

Keywords

Transverse myelitis; Neuralgic amyotrophy; Immune-mediated brachial plexopathy; Parsonage-Turner syndrome; Brachial plexus; Alpha motor neuron; Lower motor neuron

Introduction

Neuralgic amyotrophy (NA), also known as immune-mediated brachial plexopathy or brachialplexitis, is characterized by an initial period of neuropathic pain followed by paresis and paresthesiasin a peripheral nerve distribution, commonly the brachial plexus, but can also involve the lumbo-sacral plexus, phrenic nerve, recurrent laryngeal nerve, cranial nerves, or even the distal autonomicnervous system (van Alfen 2011). There are two forms of NA: idiopathic neuralgic amyotrophy(INA), also known as Parsonage-Turner syndrome, and hereditary neuralgic amyotrophy (HNA)(van Alfen and van Engelen 2006). Though the etiology is not completely elucidated, an

*Email: [email protected]

*Email: [email protected]

The Pediatric Upper ExtremityDOI 10.1007/978-1-4614-8758-6_32-1# Springer Science+Business Media New York 2014

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inflammatory-immune-mediated process is suspected for both. This theory is supported by biopsiesof affected brachial plexi containing inflammatory infiltrates as well as the commonly reportedantecedent immunization or infection, either bacterial or viral (Suarez et al. 1996; van Alfenet al. 2000a). HNA, which is autosomal dominant in inheritance, is linked to a mutation in theSEPT9 gene on chromosome 17q25 (van Alfen 2007). Both forms of NA are quite rare with theestimated overall incidence of INA being 2–3/100,000 people/year (MacDonald et al. 2000). Theratio of male to female is 1.8:1; median age of onset has been reported to be 3 years of age. There isno predisposition to side of the body involved. The epidemiological data on INA in children islimited because of the clinical similarities to poliomyelitis, resulting in misdiagnosis. HNA, evenrarer, has been described in only approximately 200 families worldwide (van Alfen 2007). Witha complete history, there is usually a parent with the diagnosis or a history of similar symptoms;however there are sporadic cases, though the incidence is unknown. Onset of HNA is usually duringthe second or third decade of life (van Alfen et al. 2000).

Transverse myelitis (TM), on the other hand, is a spinal cord disorder characterized by abruptonset of motor, sensory, and autonomic disturbances thought to be secondary to a demyelinatinglesion of the spinal cord across one or multiple segments. It is generally classified as idiopathic TMor disease-associated TM, which is linked to connective tissue diseases such as systemic lupuserythematosus (SLE) and Sjögren’s syndrome (SS), as well as other disorders of the central nervoussystem such as multiple sclerosis (MS), acute demyelinating encephalomyelitis (ADEM), orneuromyelitis optica (NMO). In some cases, initial presentation may indicate TM, though patientsprogress to develop optic neuropathy in the case of NMO or patchy lesions throughout the centralnervous system over time and space as in the case of MS (Borchers and Gershwin 2011). Diagnosticcriteria for idiopathic TM established by the Transverse Myelitis Consortium Working Group(TMCWG) include the presence of sensory, motor or autonomic dysfunction attributable to thespinal cord, bilateral signs or symptoms, clearly defined sensory level, exclusion of compressiveetiology with inflammation of the spinal cord evidenced in the cerebrospinal fluid (CSF), serum orgadolinium enhancement on magnetic resonance imaging (MRI), and progression to nadir between4 h and 21 days following the onset of symptoms (Transverse Myelitis ConsortiumWorking Group2002). Though the etiology is unknown, it also is thought to be immune-mediated as evidenced bythe immune infiltrates in the spinal cord, cerebrospinal fluid, and serum. In the general population,the incidence of new cases is 1–8/1,000,000, 20 % of which are in children (Wolf et al. 2012). Thereis a bimodal distribution with peaks in incidence in children from birth to 2 years of age and5–17 years of age (Pidcock et al. 2007). There is conflicting evidence of female to male predom-inance in children.

Usually an upper motor neuron lesion disorder, a subgroup of children diagnosed with TM byCSF, and MRI findings have been identified as having a distinct recovery pattern resulting in lowermotor neuron (LMN) injury (Sadowsky et al. 2011). These children recover function in all except forone extremity resulting in a flaccid monoplegia. The upper extremity is usually involved in a polio-like syndrome, though lower extremity cases have also been reported (Liao et al. 2007). Similar toNA, they develop weakness and rapidly progressive atrophy. Some patients may have intact sensoryfunction. This is thought to be secondary to either involvement of the alpha motor neuron of theventral spinal cord or of the proximal nerve roots resulting in a LMN type presentation and thusclinically similar to NA (Sadowsky et al. 2011).


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Pathoanatomy and Applied Anatomy

Basic Spinal Cord AnatomyPatients with TM have spinal cord involvement, which, depending on the extent of the demyelin-ation, may include the alpha motor neuron. The ventral grey matter of the spinal cord contains thecell body of the alpha motor neuron, which exits the spinal cord via the ventral root. See Fig. 1. Thisventral (motor) root connects with the dorsal (sensory) root to form a spinal nerve root. NA does notinvolve pathology of the spinal cord.

Basic Peripheral Nerve and Brachial Plexus AnatomyOnce the ventral and dorsal nerve roots exit the spinal cord, they form the spinal nerve roots, whichjoin in the periphery to form the plexus or continue on as peripheral nerves. The majority of NApatients present with brachial plexus involvement. However, the lumbosacral plexus, phrenic nerve,recurrent laryngeal nerve, cranial nerves, and the distal autonomic nervous system may be involved,especially in HNA. The brachial plexus, Fig. 2, formed from the cervical spinal nerve roots C5, C6,C7, C8, and T1, provides the sensory and motor innervation for the upper extremity. It is locatedbetween the neck and axilla, proximally between the anterior and middle scalene muscles anddistally just posterior to the clavicle and pectoralis muscles.

The plexus is divided into roots, trunks, divisions, cords, and branches moving distally. The nerveroots C5, C6, C7, C8, T1, and variably C4 and T2 descend from the spinal cord through the neuralforamen into the neck to form the plexus. C5 and C6 form the upper trunk, C7 the middle trunk, andC8 and T1 the lower trunk. The trunks descend and each branches into an anterior and a posteriordivision. The anterior divisions of the upper and middle trunks join to form the lateral cord. Theposterior divisions from the upper, middle, and lower trunk join to form the posterior cord. Theanterior division from the lower trunk continues on to form the medial cord. Off of the lateral cordbranch the lateral pectoral nerve and the musculocutaneous nerve. It also joins the medial cord toform the median nerve. The posterior cord continues on to become the radial and axillary nerves.The medial cord continues on to become the ulnar nerve (Preston and Shapiro 2005).

On a more cellular level, these peripheral nerves are made up of a layer of connective tissueimmediately surrounding the myelin sheath of an axon, called the endoneurium. The endoneurium-covered nerves are further grouped together and covered by another layer of connective tissue, the

Fig. 1 The spinal cord is comprised of ventral and dorsal white and grey matter. The ventral grey matter of the spinalcord contains the alpha motor neuron. (Reproduced with kind permission from Marion Murray and Springer Science +Business: Neuroscience in Medicine, Chapter 12, 2008, page 209, Murray M, Figure 13)


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perineurium. The perineurium-covered nerves are then grouped together and covered by a final layerof connective tissue, the epineurium, to form a nerve.

Inflammatory and Autoimmune EtiologyThe pathophysiology of NA, though not completely understood, is thought to be inflammatory andautoimmune in nature. There may also be a mechanical component related to local repetitive trauma.

On a cellular level, biopsies of affected brachial plexi demonstrate mononuclear inflammatoryinfiltrates, mainly T-lymphocytes, surrounding the epineurial and endoneurial vessels (Suarezet al. 1996). This inflammatory infiltration causes patchy damage to the brachial plexus and othernerves leading to the characteristic presentation of patchy and severe neuropathic pain followed bymuscle paralysis.

It is often preceded by a viral or bacterial infection, such as an upper respiratory infection.A history of immunization, serum therapy, pregnancy, childbirth, or surgery may also antecedesymptoms. With any of the aforementioned, the body may produce an inappropriate immune-mediated response against the brachial plexus resulting in nerve inflammation and subsequent injury(van Alfen et al. 2000a).

In addition to inflammatory and autoimmune pathophysiology, both INA and HNA can be relatedto local trauma to the neck involving the brachial plexus. On a more cellular level, local trauma can

Dorsal Scapular

Nerve to Subclavius

Suprascapular

Medial Pectoral

Lateral Pectoral

Axillary

Musculocutaneous

Radial

MedianUlnar

Medial Antebrachial Cutancous(Medial cutaneous nerve to the forarm)

Medial Brachial Cutaneous(Medial cutaneous nerve to the arm)

Lower Subscapular

Thoraeodorsal(middle subscapular)

Upper Subscapular

Long Thoracie

T1

C8

C7

C6

C5

C4

Fig. 2 Cervical and thoracic nerve roots form the brachial plexus by branching into the upper, middle, and lower trunks,then on to the anterior and posterior divisions, which further merge to become the lateral, medial, and posterior cords.The cords then branch into the peripheral nerve distributions, the musculocutaneous, axillary, radial, median, and ulnarnerves (Reproduced with kind permission from Marios Loukas and Springer Science + Business Media: Surgical andRadiologic Anatomy, The prefixed and postfixed brachial plexus: a review with surgical implications, volume 32, issue3, 2010, page 253, Pellerin M, Kimball Z, Tubbs RS, Nguyen S, Matusz P, Cohen-Gadol AA, Loukas M)


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weaken the perineurium resulting in focal damage to the individual fascicles of the nerve subse-quently resulting in the scattered pattern of motor and sensory involvement (van Alfen 2011).

Similarly, idiopathic TM is thought to be autoimmune in nature with multiple theories ofpathophysiology, all of which culminate in the demyelination and neuronal injury of the spinalcord. Infiltrates in the spinal cord in patients with TM include monocytes and CD4+ and CD8+lymphocytes, which are thought to lead to necrosis and cavitation of the spinal cord. The theory ofmolecular mimicry is evidenced in the often preceding infection (Lyme’s disease, HIV, mycoplasma,herpes virus, syphilis, and other central nervous system infections) leading to anti-GM1 antibodiesand the subsequent attack by the body’s own immune system. The theory of superantigens is thatcertain infections induce T-cells against myelin causing destruction of the spinal cord. There mayalso be humoral-mediated dysregulation leading to increased IgE causing an allergic response andfurther tissue destruction. Finally, IL-6 released from astrocytes and microglia bind to oligoden-droglia and axons causing activation of nitric oxide synthetase leading to tissue damage of the spinalcord (Wolf et al. 2012).

In addition to the aforementioned, disease-associated myelitis is found in conjunction witha number of autoimmune diseases such as sarcoidosis, Behçet’s disease, Sjögren’s syndrome,connective tissue disorders, and systemic lupus erythematosus. There is also a spectrum of inflam-matory demyelinating disorders of which TM is a part of, in addition to NMO, MS, and ADE-M. NMO is defined as transverse myelitis found in conjunction with optic neuropathy. NMO isa well-known autoimmune disorder and is associated with AQP4, aquaporin, antibodies. Acutemyelitis may also be the presenting symptom in MS, and thus children may be initially diagnosedwith TM only to further go on to be diagnosed with MS upon further imaging or anotherdemyelinating episode. Similar and yet distinct, there is now a recurrent form of acute TM, makingthis distinction sometimes difficult (Borchers and Gershwin 2012).

Assessment

Signs and SymptomsThe majority of children with NA present after a viral upper airway infection, osteomyelitis of theshoulder or humerus (most commonly seen in neonates), or vaccination. Two thirds of childrenpresent with severe neuropathic pain in the shoulder or arm, which is consistent with adultpresentation. The other third present with painless weakness and atrophy of the shoulder girdle or,less often, more distal muscles of the upper extremity (van Alfen et al. 2000a). If present, the initialpain may last approximately 2–3 weeks followed by patchy paralysis and atrophy of the musclesinnervated by the affected nerves (Tsairis et al. 1972). One should consider other etiologies such astumor, which can infiltrate local lymph nodes resulting in compression of the brachial plexus, directinfiltration of the nerve by lymphoma or leukemia, as well as primary nerve sheath tumors such asschwannomas, neurofibromas, or neurofibrosarcomas. These usually result in more insidious onsetof pain, paresthesias, and muscle atrophy, but should be considered in the differential diagnosis.

TM is also often preceded by infection but less commonly following vaccination (Wolfet al. 2012). The most frequent initial symptoms are fever; pain in the back, extremities, andabdomen; ascending numbness and weakness; walking difficulty; balance problems; and loss ofbowel and bladder control (urinary retention and/or constipation). The distribution of these symp-toms is dependent on the spinal level of the lesion as well as the area of the spinal cord involved.Cervical cord lesions present with upper extremity as well as lower extremity weakness and sensorydeficits; lower thoracic and lumbar lesions result in lower extremity weakness and numbness only.


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Initial sensory loss and weakness are ascending and may present similarly to Guillain-Barrésyndrome. If the posterior columns are involved, the child may have fine motor dyscoordinationleading to ataxia (Borchers and Gershwin 2011; Wolf et al. 2012). In the subgroup of children withalpha motor neuron involvement or root level involvement, the typical signs and symptoms may bepresent initially, but are followed by recovery of all except one limb, which remains flaccid, atrophic,and areflexic (Sadowsky et al. 2011).

In the initial phase of TM, patients often present in spinal shock with absent deep tendon reflexes(DTRs) and interruption of the sympathetic flow through the spinal cord resulting in bradycardia andhypotension. Spinal shock generally resolves in a period of days to 12 weeks with return of DTRsand signs consistent with UMN findings including hyperreflexia, Babinski’s reflex, and increase inmuscle tone.

With lesions above T6, there is a risk of autonomic dysreflexia. Other signs and symptoms involveurinary retention secondary to disruption of the connection between the pontine micturition centerand the sacral spinal cord. Constipation is also a potential complication of neurogenic bowelsecondary to decreased motility.

Physical examination in a patient suspected to have NA includes a complete generalized exam-ination including overall appearance as well as evaluation for hypotelorism or other facial dysmor-phic features, which are associated with HNA (Jeannet et al. 2001).

Head, eyes, ears, nose, and throat evaluation must be completed to look for signs of viral orbacterial infection, which may precede the onset of pain and weakness in NA and TM. In NA,evaluate speech for possible dysphonia with recurrent laryngeal nerve involvement. Palpation of theneck to evaluate for mass lesions of the brachial plexus is pertinent as well. This should be followedby a complete cardiovascular and respiratory examination, as involvement of the phrenic nerve mayresult in diaphragm paralysis and result in paradoxical breathing patterns. Also look for vasomotorsymptoms such as edema, nail and hair changes, and temperature dysregulation (Fig. 3).

General examination should be followed by a full neurologic and musculoskeletal examination.Start the neurologic examination by testing the function of the cranial nerves I-XII as NAmay affectthese. One should then test sensation to light touch and pinprick in both a dermatomal fashion to ruleout cervical cord or root pathology, but also in the peripheral nerve distribution to evaluate for plexusor peripheral nerve injury. DTRs and other primitive reflexes should be assessed to evaluate forhyperreflexia or hyporeflexia to determine if there is UMN or LMN involvement. Peripheral nervelesions resulting from NA should only be associated with lower motor neuron findings. In TM, themajority of cases may have UMN signs, though some cases may present with alpha motor neuroninvolvement resulting in LMN exam findings (Fig. 4).

Manual muscle testing should be completed and classified. One may use the Hospital for SickChildren Active Movement Scale (Tables 1 and 2). Scoring ranges from 0 to 5 with 0 ¼ no musclecontraction with gravity removed, 1 ¼ flicker of movement with gravity removed, 2 ¼ less than50 % range of motion (ROM) with gravity removed, 3 ¼ greater than or equal to 50 % ROM withgravity removed, 4¼ full ROMwith gravity removed, and 5¼ less than 50 % ROM against gravity.

The musculoskeletal examination begins with inspection of the child for edema, ecchymosis,deformity, scar, rash, or atrophy. It is important also to evaluate muscle bulk, scapular positioning,arm positioning (abduction, adduction, internal rotation, external rotation), and the child’s posture atrest and with movement. Palpation starts with the bony structures including the sternal notch, thesternoclavicular joint, along the clavicle to the acromioclavicular joint, and on to the greater andlesser tuberosities of the humerus. From here palpate the coracoid process, the suprascapular fossa,and along the spine of the scapula. To examine the scapula, ask the child to flex both arms and pushagainst a wall. Evaluate scapular movement; if the scapula wings medially, then the serratus anterior


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(innervated by the long thoracic nerve) is likely weak and/or atrophic, resulting in unopposed middletrapezius (innervated by CN XI) action (Fig. 5).

With abduction of the arm, a laterally deviating scapula is indicative of upper trapezius weaknessand unopposed serratus anterior muscle. Special musculoskeletal tests to evaluate supraspinatusmuscle impingement or bicipital tendinitis should be considered to rule out other soft tissue-relatedcauses (Malanga and Nadler 2006). In addition to the aforementioned musculoskeletal examination,

Fig. 3 Ten-year-old male with recurrent hereditary neuralgic amyotrophy (HNA) (Courtesy of Shriners Hospital forChildren, Philadelphia). (a) Episode with right-sided weakness. (b) Typical facial features with considerablehypotelorism. (c) Decreased shoulder abduction and wrist drop. (d) Limited ability to grasp


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Table 1 The active movement scale and myotomal distribution (Leis 2010)

Action MusclesMyotomaldistribution

Shoulderabduction

Middle deltoid, supraspinatus C5, C6

Shoulderadduction

Pectoralis major, latissimus dorsi, teres major, coracobrachialis, infraspinatus, longhead of the triceps, anterior and posterior deltoid

C5, C6, C7,C8, T1

Shoulder flexion Anterior deltoid, pectoralis major, biceps brachii, coracobrachialis C5, C6, C7,C8, T1

Shoulder externalrotation

Infraspinatus, teres minor, posterior deltoid, supraspinatous C5, C6

Shoulder internalrotation

Subscapularis, pectoralis major, latissimus dorsi, anterior deltoid, teres major C5, C6, C7,C8, T1

Elbow flexion Biceps brachii, brachialis, brachioradialis, pronator teres C5, C6, C7

Elbow extension Triceps, anconeus C6, C7, C8, T1

Forearmsupination

Biceps brachii, supinator C5, C6

Forearmpronation

Pronator quadratus, pronator teres, flexor carpi radialis C6, C7, C8, T1

Wrist flexion Flexor carpi ulnaris, flexor carpi radialis, palmaris longus, flexor digitorumsuperficialis, flexor digitorum profundus, flexor pollicis longus

C6, C7, C8, T1

Wrist extension Extensor carpi ulnaris, extensor carpi radialis longus, extensor carpi radialis brevis,extensor digitorum communis, extensor digiti minimi, extensor indicis, extensorpollicis longus

C6, C7, C8, T1

Finger flexion Flexor digitorum superficialis, flexor digitorum profundus, lumbricals, dorsal andpalmar interossei, flexor digiti minimi

C7, C8, T1

Finger extension Extensor digitorum communis, extensor indicis proprius, extensor digiti minimi C7, C8

Thumb flexion Flexor pollicis brevis, flexor pollicis longus, opponens pollicis, adductor pollicis C8, T1

Thumb extension Extensor pollicis longus, extensor pollicis brevis, abductor pollicis longus C7, C8

Fig. 4 A 3-year-old child with residual flaccid monoplegia of the left upper extremity related to transverse myelitisinvolving the alpha motor neuron of the ventral spinal cord. Muscle atrophy and circumferential and length differencescan be present. This is postsurgical intervention, as evidenced by the surgical scar on the anteromedial arm (Reproducedwith permission from Sadowsky et al. (2011))


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the Mallet classification, the Toronto Test Score, and the Active Movement Scales (AMS), asmentioned above, may be used to measure active movement of the upper extremity (Bae et al. 2008).

Imaging and Other Diagnostic StudiesDiagnosis of NA is made with a combination of blood work, imaging studies, and electrodiagnosticstudies, though it remains a diagnosis of exclusion. Laboratory studies, though unnecessary fordiagnosis, may show mildly elevated creatine kinase and elevated liver function tests. Other signs ofprior infection, such as viral titers or antibodies, may be positive. As in other autoimmune disorders,antiganglioside antibodies may also be present in the serum. Cerebrospinal fluid (CSF) studies inNA are generally normal, except for slightly increased CSF protein (van Alfen 2007).

In addition to the aforementioned laboratory studies, imaging studies may also contribute to thediagnosis not only by ruling out other pathologies but also in findings consistent with NA. Imagingmay begin with a basic chest X-ray to evaluate for the presence of a mass lesion or for elevation ofthe diaphragm as seen with phrenic nerve involvement. For further evaluation, magnetic resonanceneurography (MRN) of the neck to evaluate the plexus directly and MRI of the shoulder to evaluatethe musculature are appropriate. The MRN of the brachial plexus may demonstrate T2-signal

Fig. 5 Fourteen-year-old female with neuralgic amyotrophy affecting the right long thoracic nerve (Courtesy ofShriners Hospital for Children, Philadelphia). (a) Right scapular winging exacerbated by pushing against wall. (b)Side view with marked scapular winging

Table 2 Hospital for sick children active movement scale

Muscle grade Definition

0 No muscle contraction with gravity removed

1 Flicker of movement with gravity removed

2 Less than 50 % range of motion (ROM) with gravity removed

3 Greater than or equal to 50 % ROM with gravity removed

4 Full ROM with gravity removed

5 Less than 50 % ROM against gravity


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enhancement or focal thickening of the plexus (van Alfen and van Engelen 2006). MRI of the neckand shoulder may show denervation of affected muscles with findings of intramuscular edema,muscular atrophy, and fatty infiltration. The most commonly affected muscles seen on MRI are thesupraspinatus and the infraspinatus. Though it is not completely defined, in the acute phase ofdenervation, there may not be positive findings on MRI. The first sign may be diffuse increasedsignal related to edema seen on T2-weighted images of involved musculature (Scalf et al. 2007).

Diagnostic criteria for TM have been defined by the TMCWG as described previously and includeimaging, CSF studies, and serological studies. Serum evaluation includes mycoplasma antibodies,West Nile Virus titers, Bartonella henselae titers, and Lyme titers to evaluate for infection. Rheu-matological blood work should include rheumatoid factor, antinuclear, anti-double-stranded DNA,anti-single-stranded DNA, anti-RNP, anti-smooth muscle, anti-SSA, anti-SSB, andantiphospholipid antibodies to evaluate for autoimmune disorders. Aquaporin-4 antibodies orNMO IgG for the possibility of NMO-associated myelitis. CSF studies should demonstratepleocytosis or increased IgG. CSF cultures should be sent to rule out for infectious myelitis (Wolfet al. 2012).

MRI of the spine demonstrates pathology in 78 % of cases of clinical TM with lesions mostcommonly in the cervicothoracic region of the spinal cord (Fig. 6). Some patients have multifocallesions, though more commonly they are singular lesions. Two thirds of lesions involve the graymatter only and one third both gray and white matter. The majority of lesions span three or moresegments of the spinal cord, and in the acute phase, 19.1–62.5 % enhance with gadolinium (Alperet al. 2011; Sellner et al. 2009).

Electrodiagnostic studies such as nerve conduction studies (NCS) and electromyography (EMG)may be useful in diagnosing NA, when performed 10–14 days after onset of symptoms to avoid falsenegatives. NCS may show normal to slightly prolonged conduction velocities with or withoutdecreased amplitude of the sensory nerve action potentials (SNAP) and compound motor actionpotentials (CMAP). EMG may show axonal loss secondary to acute denervation with fibrillations,positive sharp waves, and polyphasic high-amplitude motor unit action potentials (MUAP). Thereare rare instances, however, that demonstrate a pattern of demyelination instead of axonal loss(Vassallo et al. 2010). Since TM is generally an UMN disease process, it usually would notdemonstrate any findings on EMG. However, in the subset of patients with flaccid monoplegiaresulting from damage to the alpha motor neuron, NCS/EMG may demonstrate a severe motorneuronopathy with acute and chronic denervation findings (Sadowsky et al. 2011).

Fig. 6 T2-weighted imaging of the cervical spinal cord of child with residual flaccid monoplegia after idiopathic TMwith cervical cord inflammation involving the alpha motor neuron. (a) Longitudinal involvement of the cervical spinalcord from C3 through C7. (b) Involvement of the ventral spinal cord and thus the alpha motor neuron (Reproduced withpermission from Sadowsky et al. (2011))


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Associated InjuriesThe initial pain associated with NA infrequently persists, but a small subset of children may go on todevelop a chronic pain syndrome with either neuropathic or musculoskeletal-type pain ora combination of the two. The musculoskeletal pain may be related to the atrophy and resultantcompensatory mechanisms and poor body mechanics necessary for the child to function as normallyas possible (van Alfen 2007). The neuropathic pain may be a continuation of the pain at initial onset.In HNA, there is a subset of patients that have a relapsing and remitting disease course withexacerbations every 6½ years resulting in pain and musculoskeletal dysfunction.

TM-associated injuries in the acute phase of the disease process may include loss of upper airwaypatency and dysphagia secondary to cranial nerve IX (glossopharyngeal nerve) involvement in theinnervation of the pharyngeal muscles. Dysphagia may also be related to longitudinally extensivelesions with extension into the brainstem. If the spinal lesion is above C5, weakness of thediaphragm may ensue, leading to respiratory difficulty. In the longer term, if the lesion is aboveT6, there is a risk of autonomic dysreflexia (AD), which is a sympathetic discharge resulting froma noxious stimuli below the level of the injury (such as distended bladder or stool impaction) andresulting in hypertension, sweating, headache, goose bumps, and flushing. This is a medicalemergency and is treated by removing the noxious stimulus and, if no improvement, lowering theblood pressure with pharmacological agents per published guidelines (Consortium for Spinal CordMedicine 2011; Wolf et al. 2012).

ClassificationNA is divided into two distinct categories: idiopathic and hereditary neuralgic amyotrophy. INA, themore common of the two, presents, as mentioned above, with severe pain usually in the shoulderfollowed by muscle paresis, atrophy, and sensory deficits. This is a singular episode that resolvesover the course of months to years.

HNA, an autosomal dominant form of NA linked to a mutation in the SEPT9 gene on chromo-some 17q25, is set apart by its recurring attacks of the characteristic acute severe pain. This is alsofollowed by muscle weakness, atrophy, and sensory deficits. It predominantly involves the brachialplexus but may also affect the lumbosacral plexus, cranial nerves, phrenic nerve, recurrent laryngealnerve, and the autonomic nervous system or a combination. Any further differences are discussedthroughout the chapter.

TM is classified in a number of ways. It is classified as disease-associated transverse myelitiswhen found in conjunction with signs and symptoms of MS, ADEM, NMO, and rheumatologicconditions such as SLE or antiphospholipid antibody syndrome. Idiopathic TM is a diagnosis ofexclusion and accounts for the majority of pediatric cases of TM (Wolf et al. 2012).

It can be further classified as acute partial TM (APTM), acute complete TM (ACTM), andlongitudinally extensive TM (LETM), based on MRI findings. APTM is defined by lesions of thespinal cord on MRI that are asymmetric, patchy, and span fewer than two vertebral segments withresultant mild to moderate weakness, asymmetric sensory loss, and possible bladder involvement.These patients may go on to develop MS with multiple lesions separated over time and spacethroughout the central nervous system. ACTM results in moderate to severe symmetric sensory andmotor deficits secondary to lesions that span the spinal cord. LETM is defined as a longitudinallyextensive lesion that spans at least three vertebral segments. These patients, though at very low riskfor developing MS, have a high possibility of progressing to NMO. Often the first lesion in NMO isa longitudinally extensive spinal cord lesion; thus aquaporin-4 (or NMO IgG) antibodies areimportant diagnostic tools in these patients. Relapse of TM may be more common in APTMcompared to ACTM as well as in LETM with a diagnosis of NMO. Recurring TM is very rare.


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Therefore patients should have a reevaluation by an experienced neurologist to assess for possibilityof additional progression or diagnosis of MS, since this may impact function and prognostication(Borchers and Gershwin 2012).

Outcome ToolsThe Functional Independence Measure in Children (WeeFIM®) and the Modified Rankin Scale(MRS) are general functional measures used in children to determine the level of independence indaily life activities. The WeeFIM® measures self-care (eating, grooming, bathing and dressing),sphincter control (toileting, bowel and bladder management), transfers (chair/wheelchair, toilet,tub/shower), locomotion (walk, wheelchair, crawl, stairs), communication (comprehension, expres-sion), and social cognition (social interaction, problem solving, memory). WeeFIM® levels rangefrom complete independence all the way to total assistance on a seven-point scale. This is used inchildren with NA and TM to determine their general level of function as it pertains to their daily life(Msall et al. 1994). The MRS, developed for adults, may also be used as a general measure offunction and ranges from 0 ¼ no symptoms at all; 1 ¼ no significant disability despite symptoms,able to carry out all usual duties and activities; 2 ¼ slight disability, unable to carry out all previousactivities, but able to look after own affairs without assistance; 3 ¼ moderate disability, requiringsome help, but able to walk without assistance; 4 ¼ moderately severe disability, unable to walkwithout assistance and unable to attend to own bodily needs without assistance; 5 ¼ severedisability, bedridden, incontinent, and requiring constant nursing care and attention; and 6 ¼ dead.

Measures of upper extremity function include the Shriner’s Hospital for Children Upper Extrem-ity Evaluation (SHUEE), the Melbourne Assessment of Unilateral Upper Limb Function (MUUL),the Quality of Upper Extremity Skills Test (QUEST), the Active Movement Scale (AMS), and theBox and Block Test (BBT). See Table 3 and Chapter 4 for details on these functional measures.

Treatment Options

Nonoperative ManagementOnly anecdotal evidence for the treatment of NA exists (Fig. 7). Nonoperative treatment measuresinclude high dose systemic corticosteroids, intravenous immunoglobulin (IVIG), and medical

Table 3 Upper extremity functional tests

Test Population Characteristics Study

SHUEE Congenitalhemiplegia

Video-based, evaluates spontaneous and “on-demand” activity Davidset al. (2006)

MUUL Congenitalhemiplegia

Evaluates range of motion, target accuracy, fluency and quality of reaching,grasping, pointing, manipulating, and releasing

Spirtoset al. (2011)

QUEST Congenitalhemiplegia

Evaluates dissociated movement, grasp, protective extension, and weight-bearing

Thorleyet al. (2012)

AMS Brachial plexusbirth palsy

Measure of joint movement in gravity-eliminated and against-gravitypositions

Curtiset al. (2002)

BBT Congenitalhemiplegia

Patient moves blocks from one side of box, over a divider to the other sidewhile measuring the number of blocks lifted, carried, and released in oneminute

Sunget al. (2005)

Brachial plexusbirth palsy

Mulcaheyet al. (2012)

These tests are used to evaluate the pediatric upper extremity function using a combination of range of motion, exercisesand functional tasks


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management of pain (Moriguchi et al. 2011; van Eijk et al. 2009; van Alfen 2009b). Systemiccorticosteroids and IVIG have demonstrated some slowing of disease progression and improvementin symptoms used either separately or together, but only in case reports and case series (Naitoet al. 2012). Pain management acutely with a long-acting nonsteroidal anti-inflammatory drug(NSAID) and a sustained release opiate are appropriate. During the subacute and chronic phasesof treatment, persistent neuropathic pain may be treated with gabapentin, carbamazepine, oramitriptyline.

The American Academy of Neurology’s evidence-based guideline for clinical evaluation andtreatment of TM is the standard of practice. Though there is insufficient evidence to support the useof corticosteroids, the first-line treatment of TM is high-dose methylprednisolone for 3–7 days.

Acute illness

Steroids

Improvement in signsand symptoms

No improvement insigns and symptoms

IVIG

MRI

RehabilitationMeasures

3 month follow up





Enhancement

Further Neurologyconsultation forsteroids/PLEX/

immunosuppressants

No enhancement

Rehabilitationmeasures

TM

NA

TM, NA

PLEX

TMNA

TM, NA

Upper ExtremityDysfunction

6 month follow up



Rehabilitationmeasures

Surgicalconsiderations

Fig. 7 Decision tree for the management of upper extremity dysfunction after transverse myelitis or neuralgicamyotrophy


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Intravenous methylprednisolone is started at 30 mg/kg/day with a maximum dose of 1 g/dayfollowed by a taper of 1 mg/kg/day over the course of 3–4 weeks (Scott et al. 2011). If noimprovement, or clinical worsening over 24–48 h after initiating steroid treatment, general practicewill warrant consideration of plasmapheresis treatment. Plasmapheresis may be effective in patientswith demyelinating diseases who have failed treatment with high-dose corticosteroids (Scottet al. 2011). Studies of immunosuppressive agents such as rituximab have shown the possibilityof decreasing TM attacks. Use of antineoplastic agents such as mitoxantrone has insufficientevidence in decreasing attacks of TM. Other agents reported in the literature with insufficientevidence for efficacy include azathioprine, cyclophosphamide, and intravenous immunoglobulin(IVIG) (Scott et al. 2011).

Indications/ContraindicationsConsidering that there is such little literature to support the use of the aforementioned in treatment ofNA, there are no specific indications or contraindications at this time. Further research must becompleted.

Indications for the use of high-dose corticosteroids in the treatment of TM include diagnosis basedon the diagnostic criteria laid out by the TMCWG. If there is no clinical improvement, or if there isclinical worsening 24–48 h after initiating steroid treatment, this is an indication to treat withplasmapheresis, though there is little evidence to support its effectiveness (Scott et al. 2011). Theuse of immunosuppressants is not defined as there is insufficient evidence to support their efficacyand use in the treatment of TM (Scott et al. 2011).

Rehabilitation TechniquesThe general rehabilitation approach for patients with NA and TM is an interdisciplinary approach inwhich there is a team of physicians, nurses, and therapists working together towards the commongoals of improvement in function for the patient. This team includes the physiatrist (rehabilitationphysician), other medical specialists (such as a neurologist), rehabilitation nursing, physical thera-pist, and occupational therapist. Other members may include a behavioral psychologist and/orneuropsychologist. Rehabilitation begins in the acute period of NA and TM with pain controlthrough the use of modalities and other techniques and continues on through the progression of thedisease as the child develops muscle weakness and atrophy leading to disability. The goal ofrehabilitation as the disease progresses is to improve function in order to promote independenceand minimize medical and physical complications which could be associated with the diseaseprocess. See Table 4 for the rehabilitation team composition and breakdown of responsibilities.

Occupational therapists play a pivotal role in the rehabilitation of children with NA and TM withupper extremity involvement. In the acute period, use of desensitization, contrast baths, focusedimagery, and cognitive behavioral therapy may help with neuropathic pain. Superficial as well asdeep heat with ultrasound may help with musculoskeletal pain. Once the child has developedweakness and atrophy of the musculature, range of motion of the shoulder, stretching and splintingare important to prevent joint contractures. To improve weakness directly, use of strengtheningexercises and neuromuscular electrical stimulation (NMES) may be useful. NMESmay be valuable,not only for active range of motion but also for assisting in muscle contraction and retraining.Biofeedback throughout the rehabilitation process may improve awareness of the ongoing physio-logic processes (Ramos and Zell 2000; Tables 5, 6, 7, and 8).

From a functional standpoint, the occupational therapist and physical therapist may perform anevaluation for adaptive equipment. In those children with distal upper extremity weakness, thisincludes a universal cuff, which utensils can be attached to if the child has poor grip strength. Foam


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tubing can be used on writing and eating utensils to achieve easier grasp in patients who have morebut still limited grip strength. Poor proximal upper extremity strength may lead to difficulties withADLs. Useful adaptive equipment including a reacher, dressing stick, sock aide, long-handledsponge, or shoe horn may be utilized to maximize independence in daily activities. This mayimprove the child’s independence and may provide the opportunity to perform age-appropriateactivities such as feeding, grooming, bathing, dressing, and school activities.

Table 5 Preoperative planning for ulnar to biceps nerve transfer

Ulnar to biceps nerve transfer

Preoperative planning

OR table: regular

Position/positioning aids: standard, prep of full extremity

Fluoroscopy location: none

Equipment: Nerve stimulator, microscope, microsurgical instrumentation, fibrin glue

Tourniquet: not used

Table 6 Surgical steps for ulnar to biceps nerve transfer


Surgical steps

Linear incision along the medial aspect of the arm

Identify the median, ulnar and musculocutaneous nerves

Isolate the biceps innervation and gain length with internal neurolysis of the musculocutaneous nerve

Internal neurolysis of the ulnar nerve and identify a fascicle that on stimulation activates flexor carpi ulnaris

Divide the proximal portion of biceps innervation and rotate distal portion towards the ulnar nerve

Divide the ulnar nerve fascicle to flexor carpi ulnaris and rotate the proximal portion towards the biceps nerve

Perform an end to end coaptation of the distal biceps innervation to the proximal divided ulnar fascicle and secure withfibrin glue

Close the wound

Table 4 Rehabilitation NA

Discipline Treatment

Physiatrist Coordination of rehabilitation needs

Neurologist Assistance in work-up and management of possible inflammatory components leadingto disability and changes in function

Occupational therapist Range of motion, stretching, splinting, strengthening, NMES, adaptive equipment,desensitization, contrast baths, ultrasound

Physical therapist Adaptive equipment, functional mobility evaluation, mechanics of ambulation, andfunctional mobility

Behavioral psychology/neuropsychology

Biofeedback, focused imagery, cognitive behavioral therapy. Cognitive assessment

Rehabilitation nursing Coordination of basic medical needs

The rehabilitation team consists of a number of clinicians who all take part in treatment of the patient throughout theirrehabilitation and with the common goals of the patient


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In addition to the equipment evaluation, the physical therapist focuses on functional mobility andproper body mechanics. This is very important to prevent associated injuries to other musclesbecause of compensatory techniques. This begins with an evaluation of general mobility and gaitwith a focus on body mechanics. This is also quite important in the TM patient with motor deficits inthe lower extremities for strengthening and stretching to maintain range of motion as well as gaittraining.

OutcomesOutcomes of nonoperative treatment of NA using measures of medical stability, function, level ofpain, or quality of life are not available. The general trend of recovery in NA is 63% of children withfull recovery, 25 % with partial recovery, and 13 % that do not recover (Host and Skov 2010). Theaforementioned upper extremity functional measures are used in children with upper extremitydysfunction secondary to cerebral palsy or brachial plexus birth palsy, though they can be extrap-olated to be used in children with lower motor neuron upper extremity dysfunction secondary toNA. There is no data available in this population of children with NA using these functionalmeasures.

Prognosis in TM generally follows the rule of thirds, which states that approximately one third ofpatients have a good outcome, one third have a fair outcome, and one third have a poor outcome. Inchildren, complete recovery is achieved in 33–50 % with poor outcomes in 10–20 % of cases (Wolfet al. 2012). Treatment outcome data is not sufficient in children to make strong conclusions, but oralsteroids have been shown to result in better functional mobility outcomes. At the same time,however, some patients who did not receive treatment had better functional outcomes for ADLs

Table 7 Postoperative protocol for ulnar to biceps nerve transfer


Postoperative protocol

Suction drains are rarely required

Arm immobilized at elbow for 3–4 weeks

Gentle range of motion exercises

Reeducation instituted once reinnervation evident

Table 8 Potential pitfall and prevention for ulnar to biceps nerve transfer


Potential pitfalls and preventions

Potential pitfall Pearls for prevention

Pitfall #1 Stimulation of musculocutaneousnerve produces biceps activation

Abort the procedure and inform patient regeneration is likely occurring

Pitfall #2 Difficulty finding the bicepsinnervation

Trace the musculocutaneous nerve towards the axilla as the takeoff canbe proximal. There can be an anomalous anatomy of the lateral cordand median/musculocutaneous nerves

Pitfall #3 Failure of tension free end to endcoaptation

Gain length by continuing the internal neurolysis of biceps branch intomusculocutaneous nerve

Pitfall #4 Difficulty identifying fascicle toflexor carpi ulnaris

Separate the ulnar fascicles and lower the stimulation settings. Usea fascicle that has strong muscle contractions, minimal fingercontractions, and is located medial in the nerve


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and functional mobility than those who did undergo treatment. At follow up, 54 % of patients stillexperience dysesthesias and 75% numbness. Urinary retention persists in 50 % of children at followup, urgency in 68 %. With regard to motor function, 52 % of children who were non-ambulatory atthe nadir of their clinical course were able to ambulate with or without an assistive device (Pidcocket al. 2007). Overall, better outcomes are seen in children with normal CSF white blood cells(WBC), diagnosis within 7 days of the onset of symptoms, and lower level of injury in the spinalcord. Poorer outcomes are associated with age less than 3 years and greater extent of lesion of thespinal cord (Pidcock et al. 2007).

In our experience children with alpha motor neuron involvement resulting in flaccid monoplegiahave minimal improvement of the affected limb, despite aggressive nonoperative management.Quick onset of muscle atrophy and loss of bone mass is observed within the first month. In thegrowing child, similar to long-term effects from poliomyelitis infection, this may result in limblength discrepancy, osteoporosis with high risk for fractures, high risk for neurogenic arthropathy(often seen in patients with lower limb involvement), overuse of stronger musculature, and muscularstrain with chronic pain.

Operative Treatment of TM and NAA small subset of patients with TM and NAwill have permanent focal neurological dysfunction dueto injury within the spinal cord. When the anterior horn is involved and there is loss of anterior hornmotor neurons, the resultant injury is a LMN deficit with extensive denervation of the target muscle.There is severe atrophy and, given the loss of the motor neuron cell body, no possibility for nerveregeneration. Peripheral nerve surgeons encounter a similar scenario with traumatic avulsion ofnerves including elements of the brachial plexus.

Novel therapeutic approaches are needed to restore function in those patients facing permanentdisabilities. Traditionally, the nerve surgeon isolates the site of injury, surgically resects the injuredsegment, and restores continuity by end-to-end repair or insertion of a nerve graft. If the point ofinjury is in the spinal cord, such as seen in TM, at the level of the motor neuron cell body, there are noaxons available to reinnervate the distal nerve with. For NA, the injury can occur anywhere along theperipheral nerve, and it may not be possible to localize the injury to a particular segment.

Nerve transfers have demonstrated efficacy for restoring function in the extremities after periph-eral nerve injury (Pindrik et al. 2013). Nerve transfers may be an option to restore function in selectpatients who have isolated LMN deficits including those with TM and NA.

The aim of nerve transfer is to re-energize the injured “target” nerve with axons from a functioning“donor” nerve. The recipient nerve has crucial target muscle versus the donor nerve, and there is alsoredundancy in the innervation of the donor nerve muscle(s). The surgeon is “robbing Peter to payPaul.” In appropriately selected cases, where there is sufficient redundancy that there is no recog-nizable deficit from taking the donor fascicles, one may also transfer a single fascicle rather than theentire nerve. The most commonly performed nerve transfers include the Oberlin procedure thati transfers of an ulnar nerve fascicle to the biceps branch of the musculocutaneous nerve (Teboulet al. 2004). Another nerve transfer technique involves using a triceps nerve branch as a donor to theaxillary nerve for restoration of elbow flexion and shoulder abduction (Bertelli et al. 2007). SeeChapters 28 and 31 for details of nerve transfers.

The advantages of distal fascicle transfers include: nerve regeneration is closer to the targetmuscle, improved direction of motor axons to the target muscle, and direct transfer without the use ofinterpositional nerve grafts. In comparison to nerve repair at the point of proximal injury, the point ofcoaptation in nerve transfer is usually closer to the target muscle, and the expected time for axonalregeneration to the motor endplate is less. Distal transfers are also advantageous in cases with


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a prolonged interval between injury and surgery or when the level of injury is proximal along thenerve or in the spinal cord (Dorsi and Belzberg 2012).

The use of nerve transfer to manage patients with TM was recently reported (Dorsi and Belzberg2012). The patient had recovered median and ulnar function but lacked elbow flexion and shoulderabduction. Transfers included ulnar and median fascicle to biceps nerve and brachialis nerve,respectively. In addition, the spinal accessory nerve was transferred to the suprascapular nerve.There was excellent recovery of elbow flexion and less about the shoulder girdle.

Shorter durations of time between nerve injury and surgery offer better chances for regenerationand recovery of useful function (Pindrik et al. 2013). Prolonged delay between the inciting event andsurgical intervention may result in severe muscle atrophy and loss of support cells in the distal nerveand/or muscle. Muscle fibers atrophy and scar 12–18 months following denervation and vacantendoneurial tubes degenerate 18–24 months after Wallerian degeneration. Prolonged denervationcan prevent functional recovery despite adequate nerve regeneration across the area of injuryfollowing nerve transfer.

Persistent neurological deficits amenable to surgery will do best with the procedure performed3–6 months after injury. Nerve transfers should be attempted within 6 months after injury, or diseaseonset, to offer the best chance of successful muscle reinnervation (Pindrik et al. 2013). Therefore, anearly decision needs to be made regarding likelihood that spontaneous will or will not occur. Earlychanges on EMG reflecting nerve regeneration and muscle reinnervation include the presence ofnascent potentials. Imaging studies can demonstrate denervated muscle but have not been useful todemonstrate nerve regeneration (Pindrik and Belzberg 2014). Unfortunately, there is no currentclinical methodology to adequately predict the functional outcome for a patient 6–8 months into thediagnosis with TMwith persistent profound deficits. Decision making as to surgical intervention fornerve repair has to be individualized and should include a multidisciplinary team.

In contrast to nerve reconstruction, surgical consideration for muscle or tendon transfers can bedelayed until neurological recovery has plateaued. By transferring the tendon of a functional muscleto an alternate insertion, one can impact function in a very predictable manner. Primary surgeryusually refers to a nerve repair with secondary surgery referring to tendon or muscle transfers as wellas joint manipulations. The topic of secondary surgery is covered elsewhere in this textbook inChapter 29. For patient with TM or NA, it is critical to maintain adequate passive range joint range ofmotion throughout the recovery process. Stiff joints or shortened tendons can limit the recovery andoptions for secondary surgery.

Management of ComplicationsSystemic corticosteroids, sometimes used to treat NA and TM, may result in growth disturbance,weight gain, hyperglycemia, hypertension, cataracts, avascular necrosis, and osteoporosis in chil-dren (Table 9). These complications occur more frequently with prolonged use. Avoidance measuresinclude limiting the time on steroids to as low dose as possible and tapering the dosage as quickly aspossible while still avoiding adrenal insufficiency. Steroid-induced myopathy is another adversereaction that may lead to proximal weakness and worsening of functional impairments. Monitoringfor these side effects to prevent further complications, such as fragility fractures associated withosteoporosis caused by steroids, is important. The physician should monitor blood sugars, weight,and vision throughout the treatment course. Also, the physician should monitor for signs ofavascular necrosis, which is most common in the hip diagnosed by pain and difficulty walking(Kliegman et al. 2011).

IVIG adverse effects include fever, headache, myalgia, nausea, and vomiting, which may beremedied by decreasing the rate of infusion. More serious reactions include anaphylaxis,


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thromboembolic disorders, renal insufficiency, and aseptic meningitis, which have been described inpatients with NA and TM being treated with IVIG. This is managed by discontinuation of the IVIGinfusion (Kliegman et al. 2011).

Plasmapheresis complications include general side effects such as paresthesias, muscle cramps,nausea, vomiting, urticaria, and pruritus. More severe complications include hypotension, broncho-spasm, transfusion-related acute lung injury, hypocalcemia, metabolic alkalosis, and coagulationabnormalities. It may also deplete the child’s immunoglobulins putting them at substantial risk forinfection. Management of these complications includes symptomatic treatment for the less severeproblems and discontinuing the treatment in the more severe reactions such as the transfusion-related acute lung injury (Kaplan et al. 2012).

Immunosuppressants such as azathioprine can cause rash, stomatitis, gastrointestinal distur-bances, alopecia, and arthralgias, which may be treated symptomatically. More severe complications

Table 9 Management of complications of treatment

Treatment Common complications Management

IVIG Anaphylaxis, thromboembolic disorders, renalinsufficiency, and aseptic meningitis

Stop the infusion

Fever, headache, myalgia, nausea, and vomiting Slow the infusion

Steroids Growth disturbance, weight gain,hyperglycemia, hypertension, cataracts,avascular necrosis, and osteoporosis

Taper

Plasmapheresis Paresthesias, muscle cramps, nausea, vomiting,urticaria and pruritus, infection

Treat symptomatically

Hypotension, bronchospasm, transfusion-related acute lung injury, hypocalcemia,metabolic alkalosis, coagulation abnormalities

Stop treatment, if severe

Cyclophosphamide Hemorrhagic cystitis, nausea, and vomiting Symptomatic treatment

Leukopenia and cardiomyopathy Decrease dosage or discontinue treatment

Long term includes infertility, cardiomyopathy,secondary malignancy, andleukoencephalopathy

Surveillance

Rehabilitation Pain Ice, heat, ultrasound, desensitization,antiepileptics, tricyclic antidepressants,NSAIDs

Fragility fracture Evaluate bone density prior to aggressiverehabilitative interventions. With occurrence,stop therapies and consult orthopedics

Tendinopathies Decrease intensity of therapy, symptommanagement with thermal modalities

Surgery Infection Culture the wound and blood for appropriate useof antibiotics

Follow blood indicators ESR and C-reactiveprotein

Pain Aggressive treatment of postoperative pain

Multidisciplinary approach to neuropathic pain

Delayed presentation Very distal nerve transfer or use of free muscleflap (gracilis) with nerve transfer

Treatments of TM and NA come along with complications, though some may be treatable whereas others may result indiscontinuation of treatment


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include bone marrow suppression and hepatotoxicity. Suppression of the immune system places thechild at risk for infection. Antineoplastic agents used include cyclophosphamide, mitoxantrone, andrituximab. Used in the acute phase of treatment, cyclophosphamide may cause leukopenia andcardiomyopathy, which require either adjustment of dose or discontinuation of treatment. Other sideeffects include hemorrhagic cystitis, nausea, and vomiting. In the long-term it may lead to infertility,cardiomyopathy, secondary malignancy, and leukoencephalopathy. The milder side effects may betreated symptomatically. The longer-term side effects limit the course of cyclophosphamide use(Custer and Rau 2009).

Rehabilitative interventions may also result in complications. These include pain, fragilityfractures, and tendinopathies. Pain is a prominent feature of both TM and NA in the acute period,but also may result from musculoskeletal imbalance and poor biomechanics related to the moresubacute weakness andmuscle atrophy.Musculoskeletal-type pain may be treated with NSAIDs andice in the acute period. In the more chronic period, superficial heat and deep heat with ultrasoundmay be useful for pain management. For painful dysesthesias, one can consider use of neuropathicagents such as gabapentin or a tricyclic antidepressant such as amitriptyline. If the pain is severeenough and/or chronic, one may consider the use of opioids or more advanced pain managementstrategies, though this does not treat the source of the pain.

Fragility fractures are associated with disuse osteoporosis, which is a prominent feature of bothNA and TM. It has not specifically been documented as a complication of rehabilitation in NA, but inchildren with cerebral palsy and with TM, the muscle disuse and reduced muscle load on the bonecontribute to fracture risk (Sadowsky et al. 2011; Huh and Gordon 2013). Other predisposing factorsinclude the use of steroids as glucocorticoids promote bone resorption and reduce bone formationthrough both hormonal and cellular mechanisms. They also inhibit intestinal calcium absorption andincrease renal calcium loss. Other medications that may be used in the treatment of these patientswhich may contribute to bone loss and fractures are immunosuppressants. First and foremost,optimal bone health is highly recommended in this patient population. Hydroxyvitamin D levelsas well as calcium intake should be assessed and deficiency should be treated with replacementdoses of vitamin D3 and calcium, respectively. Patients may benefit from evaluation of bone masswith dual-energy X-ray absorptiometry (DEXA) scan prior to aggressive rehabilitation measures. Iffindings are consistent with osteoporosis or severe osteopenia, the patient should be referred forendocrinological evaluation regarding management with possible bisphosphonates to maximizebone density. If the child has a fragility fracture, rehabilitative measures should be held untilorthopedic evaluation.

Overuse injuries such as tendinopathies may occur during the course of rehabilitation, especiallywith the repetitive tasks that are performed in strengthening exercises. Though previously termedtendonitis, there is little to no inflammation, and thus anti-inflammatory medications are notappropriate treatment. Treatment would include a decrease in the intensity of therapy and avoidingcertain activities that are painful for the child while maintaining range of motion and preventingcontractures. Symptomatic treatment includes ice in the acute period followed by heat.

Summary

NA and TM, both thought to be autoimmune and inflammatory in nature, may result in upperextremity monoplegia in children. NA, most often affecting the brachial plexus, results in a LMNsyndrome and flaccidity. TM, on the other hand, may lead to spastic or flaccid monoplegiadepending on the site of the lesion. Both may be diagnosed with MRI and serological studies with


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diagnosis also supported by NCS and EMG. Initial treatment of TM is with high-dose corticoste-roids and, if no improvement, with plasmapheresis or even immunosuppressants or antineoplasticagents. Steroids may also be used for the initial treatment of NA, with little evidence for manage-ment with IVIG. Rehabilitation includes ROM, stretching, strengthening, neuromuscular electricalstimulation, techniques for pain management, education, and equipment. Outcomes may be mea-sured with theWeeFIM® and theMRS for general function and the SHUEE,MUUL, QUEST, AMS,and BBT for more focused upper extremity outcome measurement. Sixty-three percent of childrenwith NA fully recover, while 33–50 % of children with TM do. There is minimal outcomes data inNA, but children with TM are noted to have significant motor recovery with ongoing bowel andbladder dysfunction, especially during the first 3 months. For children not showing the expectedrecovery, the aggressive use of nerve transfers provides an alternative approach by providinga source of motor axons. This can be done in collaboration with muscle or tendon transfers tomaximize the unction. Future research is needed for treatment including medical management,surgical management, and rehabilitation strategies. Knowing which patient will have a poor prog-nosis for spontaneous recovery versus those who would benefit from early surgical intervention withnerve repair and possible tendon transfers remains a challenge.

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