A thorough history is vital in the evaluation of neuromuscular diseases. The presentation of a peripheral neuropathy in the pediatric population may be different from that of an adult. The nature of the chief complaint helps define the type of neuropathic process. Patients may present with weakness, sensory disturbances, pain, autonomic disturbance, atrophy, ataxia, or a combination thereof. The time course of the symptoms is an important diagnostic clue, whether it is acute, subacute, or chronic (relapsing, recurrent, progressive, and so forth). Neuropathies can present with a number of different anatomic patterns. Symmetric or asymmetric, focal or diffuse, helps differentiate between a mononeuropathy, mononeuropathy multiplex, polyneuropathy, radiculopathy, polyradiculopathy, or plexopathy.1
In the history of a neuromuscular disorder, the examiner should always ask specifically about trauma, toxic exposures (including recreational drugs and alcohol), infections or vaccinations, dietary deficiencies, medications (both past and present), and concomitant medical conditions (Table 14-1).1 Constitutional symptoms such as weight loss or unexplained fever may direct the evaluation toward an underlying etiology. Family history may be extremely important in the neuropathies seen during childhood since many of these disorders have a genetic basis.
A thorough physical examination is very important in the evaluation of neuromuscular disorders. The cranial nerves are rarely involved in a typical peripheral neuropathy but are commonly involved in Guillain–Barré syndrome (GBS), sarcoid, carcinomatosis, and diphtheria.1 Atrophy and its distribution can assist with certain diagnoses such as Charcot-Marie-Tooth disease with the classic champagne bottle legs. As with atrophy, the distribution of weakness guides diagnosis. Most polyneuropathies affect distal muscles of lower extremities first. Most demyelinating and certain acute motor and toxic neuropathies affect all muscles of limbs, trunk, neck, and some facial muscles. With the help of the history, try to narrow weakness into a pattern of mononeuropathy, mononeuropathy multiplex, polyneuropathy, radiculopathy, polyradiculopathy, or plexopathy.
While the sensory examination is very important in the assessment of a patient with a neuropathy, it may be very difficult to formally assess in children, especially the very young. Most peripheral neuropathies have distal, symmetric, sensory loss in lower extremities first (stocking-glove distribution). Sensory loss exceeds weakness in most toxic neuropathies.
The reflex examination usually reveals diminished or completely lost reflexes. The reflexes may be diminished out of proportion to the degree of weakness.1
A general skin and musculoskeletal examination is also of great importance. Pes cavus is often seen in hereditary neuropathies secondary to weakness of peroneal and pretibial muscles more than calf muscles. A “claw” hand may arise in the upper extremity for similar reasons. Kyphoscoliosis can occur secondary to weakness of paravertebral muscles. Skin ulcers, pressure sores, and burns are often seen secondary to analgesia. Analgesic joints become traumatized resulting in a deformity known as Charcot arthropathy. Hypertrophied nerves are seen in a number of neuropathies including chronic inflammatory demyelinating polyneuropathy (CIDP), Refsum disease, leprosy, hereditary sensory motor neuropathy (HMSN; III > II > I), acromegaly, neurofibromatosis, and amyloidosis.
Electrophysiologic studies (nerve conduction studies) can further categorize neuropathies as primarily demyelinating or axonal, sensory or motor, or both. This information helps to differentiate between mononeuropathy, polyneuropathy, mononeuropathy multiplex, plexopathy and radiculopathy.1
Most peripheral neuropathies are axonal and usually have symmetrical distal sensory loss with weakness, atrophy, and lost ankle jerks. The nerve conduction study shows significantly decreased amplitudes of compound motor action potential (CMAP) and sensory nerve action potential (SNAP) (often no obtainable potential), but only mild slowing without conduction block or temporal dispersion. Needle EMG shows evidence of distal denervation (frequently not performed in children).1
Demyelinating neuropathy is a less common category of peripheral neuropathy. Early generalized reflex loss, mild atrophy, proximal and distal muscle weakness, sensory loss of large fiber; small fiber modalities, motor usually; sensory involvement, tremor, and hypertrophied nerves are common physical findings in a patient with a demyelinating neuropathy. Nerve conduction studies reveal marked nerve conduction velocity slowing, conduction block, temporal dispersion, and prolonged F-wave and distal latencies. The needle EMG may show denervation, based on the chronicity of the neuropathy. GBS, CIDP, and some hereditary neuropathies are demyelinating. Many neuropathies are mixed axonal and demyelinating and mixed sensory and motor.
Laboratory studies are very important in the evaluation of neuropathy. A wide array of laboratory tests may be ordered but the exact panel depends on the history and the physical examination. Suggested laboratory studies are listed in the following sections.
Lumbar puncture is especially helpful in the diagnosis of a demyelinating neuropathy such as GBS or CIDP. In these patients, the CSF protein is elevated.
Specific treatment modalities aimed at the underlying etiology are not possible in most neuropathies (especially chronic sensory motor polyneuropathies); nevertheless, the search for a specific, treatable cause should be undertaken. In approximately 25% of all chronic polyneuropathies, an etiology cannot be determined. Treatments for specific neuropathies, such as GBS and CIDP, are discussed later in this chapter.
Acute inflammatory demyelinating polyneuropathy (AIDP) or GBS is the most frequent cause of acute generalized weakness. The incidence is 1 to 2 per 100,000 per year. It occurs in a nonseasonal, nonepidemic pattern affecting both genders, all ages, and in all parts of the world. While incidence increases with increasing age (highest ages 50-74 years), childhood cases are not unheard of.1
Two-thirds of patients have a preceding event 1 week to 1 month prior to onset (URI, 60%; GI syndrome, 20%; surgery, 5%; vaccinations, 5%).1 Antecedent infections associated with GBS are listed in Table 14-2. Lymphoma, particularly Hodgkin disease, has been associated with GBS. Surgery and spinal/epidural anesthesia may also precipitate GBS.
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Immune-mediated segmental demyelination is initiated by an undetermined antigenic reaction (possibly viral). There is a cell-mediated component in which T-cell lines are sensitized to P2, a basic protein found in peripheral nerve myelin. A clinically and pathologically indistinguishable disease called experimental allergic neuritis (EAN) develops in animals 2 weeks after immunization with a peripheral nerve homogenate containing P2.
An antibody-mediated component also occurs with immunoglobulins and complement found on myelinated fibers, and anti-peripheral nerve myelin antibodies found in some patients’ serum (titers correlate with clinical course). An antibody to the GD1a ganglioside has been associated with a worsened clinical course.
Pathology specimens show perivascular mononuclear cell infiltrates early, associated with perivenular demyelination. Later, segmental demyelination and secondary Wallerian degeneration occur, affecting entire peripheral nerves, cranial nerves, dorsal and ventral roots, and dorsal root ganglia.
Most patients present with rapidly progressive symmetrical weakness with areflexia.2 The weakness is usually ascending (distal to proximal) with the lower extremities affected first, then trunk, arms, and cranial muscles.3 In rare cases, proximal muscles can be affected first. Cranial nerves are rarely affected first, but more than 50% of patients have cranial nerve involvement, with facial diplegia being the most common deficit.
The maximum deficit typically occurs within days of onset up to maximum of 4 weeks after onset and then plateaus.3 Total motor paralysis with respiratory failure and death may occur in a few days in severe cases. Weakness is so rapid that atrophy is rarely seen. The weakness is associated with hypotonia. An acute cord lesion should be considered in patients with low back pain, areflexia, and leg paralysis. The reflexes are initially decreased and then absent in GBS.
While GBS is a motor neuropathy, sensory complaints are common.2,3 Low-back pain and myalgias occur in many patients, often involving the hips and thighs. Severe myalgias are rare and increased CPK levels should suggest other disorders. Paresthesias are a common early symptom but resolve rapidly. Objective sensory loss is usually mild and usually affects large fiber modalities (vibration and position sense).
Autonomic instability is fairly common but highly variable in expression.1-3 Patients may experience one or more dysfunctions of the autonomic system, occasionally with rapid fluctuations. Sinus tachycardia, bradycardia, other tachyarrhythmias, orthostatic hypotension, hypertension, anhidrosis, diaphoresis, sphincter dysfunction, pupil changes, gut atony, and flushing can occur. The autonomic dysfunction usually lasts less than 1 to 2 weeks. Urinary retention occurs in 15% of cases.
Clinical variants are even less common than GBS. Miller-Fisher syndrome consists of gait ataxia, ophthalmoparesis, and areflexia, with normal limbs (some patients have mild proximal limb weakness). It is associated with IgG antibody to ganglioside GQ1b and prior Campylobacter jejuni infection.4,5
Pharyngeal–cervical–brachial GBS consists of blurred vision or diplopia, ptosis, marked oropharyngeal, neck and shoulder weakness, respiratory failure, areflexia in arms only, and normal sensation (occasionally leg areflexia present). This disorder simulates botulism and diphtheria clinically. There is no dry mouth, dizziness, or GI symptoms that are typical of botulism.
Acute demyelinating inflammatory polyneuropathy is relatively uncommon in children and may mimic a variety of disorders making diagnosis a challenge. Rapid diagnosis is important as treatments are available that may help avoid complications. Table 14-3 outlines the differential diagnosis with differentiating factors.
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Nerve conduction studies reveal focal nerve conduction velocity (NCV) slowing, motor conduction block, temporal dispersion, and prolongation of F-wave and terminal latencies. All parameters may be normal for the first few days. The initial abnormality is prolonged (or absent) F-waves. Nerve conduction studies can remain normal in up to 10% of cases.9
CSF studies typically exhibit an elevated protein with normal cell count (albuminocytologic dissociation). In rare cases, patients will have 10 to 50 cells/mm3 (mostly lymphs). Protein may remain normal for the first few days, rising to peak in 4 to 6 weeks. Unfortunately, CSF protein remains normal in 10% of patients, making diagnosis even more challenging. The opening pressure and CSF glucose are usually normal.
Blood should be sent for complete blood count, metabolic profile with Ca, Mg, Phos, hepatic studies, HIV, ESR, and Lyme disease. If suggested by history, heavy metal studies should be obtained.
Supportive therapy is vital with respiratory assistance and careful nursing. Frequent forced vital capacity (FVC) measurements should be obtained. Intubation should be considered if the FVC falls below 12 to 15 mL/kg, regardless of arterial blood gas testing. If there is significant bulbar weakness even with a good FVC, the patient may need intubation for airway protection. Respiratory therapy should be consulted for aggressive pulmonary toilet. Tracheostomy may be necessary if the patient requires prolonged intubation.
Cardiac monitoring and frequent vital signs are important given the risk of autonomic dysfunction. As with all pediatric patients, special attention must be given to the fluid status.
Physical therapy should be consulted early in the hospital stay for range of motion, but the patient should not be pushed aggressively during therapy sessions, given the risk of respiratory insufficiency.
The patient must be monitored for the development of decubitus ulcers. The patient should be turned frequently to avoid the prolonged pressure leading to skin breakdown.
Artificial tears during the day, and lubricating gel with eye patches at night, should be used if there is significant facial weakness.
In mild cases, careful observation and supportive care may be all that is needed. Patients who are progressing, are ambulatory only with assistance or recently have become nonambulatory, or those with respiratory compromise or autonomic instability, should be considered for immune modulating therapy. Two treatment options exist for GBS: therapeutic plasma exchange and intravenous immunoglobulin.10-12
Therapeutic plasma exchange (TPE) is a common treatment in adults but has significant limitations in children.12 It is most effective if given within 7 days of disease onset and for patients who require intubation. Use of TPE results in decreased hospitalization time, mechanical ventilation time, and time until the patient walks again. The side effects include hypotension, bleeding, arrhythmias, and infection. The volume exchanged limits this treatment option in children.
Intravenous immunoglobulin (IVIg) was proven effective in one multicenter trial at dosage of 400 mg/ kg/d × 5 days. There appears to be a reduced complication rate over TPE, and less need for mechanical ventilation. The side effects include allergic reactions, renal failure, aseptic meningitis, increased serum viscosity with vasoocclusive phenomena, and headache. Always check an IgA level prior to IVIg initiation, given the increased risk of anaphylaxis in IgA-deficient patients when administered IVIg.10,11
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