Landry described a condition characterized by acute ascending paralysis in 1859. Later, Guillain, Barré, and Strohl noted the areflexia and the albuminocytologic dissociation in the cerebral spinal fluid (CSF) associated with this neuropathy.1 The contributions of Landry and Strohl have been neglected, and the neuropathy has been most commonly referred to as Guillain–Barré syndrome (GBS). In 1949, Haymaker and Kernohan detailed the histopathologic features seen in 50 fatal cases of GBS. The earliest features noted were edema of the proximal nerves and the subsequent degeneration of the myelin sheaths within the first week of the illness. They did not appreciate inflammatory cell infiltrate until later in the course of the illness.2 However, another group reported prominent perivascular inflammation in the spinal roots, dorsal root ganglia, cranial nerves, and randomly along the whole length of peripheral nerves, along with segmental demyelination adjacent to the areas of inflammation, in 19 autopsy cases of GBS.3 Thus, the term acute inflammatory demyelinating polyradiculoneuropathy (AIDP), which is quite descriptive of the disease process, has been historically used synonymously with GBS.4–7 It is now appreciated that GBS is not a single disorder but again a syndrome of several types of acute immune-mediated polyneuropathies (Table 13-1).8–11 In addition to AIDP, there are two axonal forms of GBS: acute motor–sensory axonal neuropathy (AMSAN) and acute motor axonal neuropathy (AMAN). Further, some disorders that appear clinically different from AIDP (e.g., the Miller Fisher syndrome [MFS] and acute autonomic neuropathy) may share similar pathogenesis and can be considered variants of GBS.
ACUTE INFLAMMATORY DEMYELINATING POLYRADICULONEUROPATHY
AIDP is the most common cause of acute generalized weakness, with an annual incidence ranging from 0.9 to 4 per 100,000 population.7,10–13 The neuropathy can occur at any age, with a peak age of onset of approximately 38–40 years. There may be a slight male predominance.
Approximately 60–70% of patients with AIDP have a history of a recent infection a few weeks prior to the onset of the neuropathy.7,10,11 A control study of 154 patients with GBS revealed serologic evidence of recent Campylobacter jejuni (32%), cytomegalovirus (13%), Epstein–Barr virus (10%), and Mycoplasma pneumoniae (5%) infection.14 The serologic signatures of these infections were more prevalent than in the control population. Other studies have also reported that 15–45% of patients with AIDP have serologic evidence of recent Campylobacter enteritis.15–22 The relationship between C. jejuni infection and the different variants of GBS (AIDP, AMSAN, and AMAN) has been the subject of many reports and is discussed in detail in the pathogenesis sections of these disorders. Other infectious agents associated with GBS include influenza, hepatitis A, B, C, and E, and human immunodeficiency virus (HIV).7,10,20,23,24 In HIV infection, AIDP usually occurs at the time of seroconversion or early in the course of the disease.
Vaccinations, most notably for swine flu, have been associated with GBS.25,26 Slightly increased risks of GBS have been associated with seasonal flu (influenza) vaccination. Most studies 27–31, but not all 32,33, have seen a slightly increased risk of GBS following H1N1 vaccination. No significant increased risk of GBS was found with meningococcus 34 and hepatitis 35 vaccinations, while one study of human papilloma virus (PPV4) revealed no increase in risk of GBS compared to other vaccinations.36
Other disorders have been associated with a possible increased risk of GBS, including other autoimmune disorders (i.e., systemic lupus erythematosus), lymphoma, organ rejection or graft versus host disease following solid organ and bone marrow transplantation, and perhaps recent surgery.10 Certain immunomodulating agents, such as tumor-necrosis alpha blockers, may increase the risk of developing GBS.37
AIDP usually presents with numbness and tingling in the feet that gradually progresses up the legs and then into the arms (Table 13-2).7,10,11,38 Numbness and paresthesia can also involve the face and trunk. Severe, aching, prickly, or burning neuritic pain sensations in the back and limbs are present in at least half the patients and may be particularly common in children. Large fiber modalities (touch, vibration, and position sense) are more severely affected than small fiber functions (pain and temperature perception). Although initial symptoms are typically sensory in nature, progressive muscle weakness quickly becomes the dominant feature in most cases. Progressive weakness typically accompanies the sensory disturbance. The severity can range from mild distal weakness to complete quadriplegia and need for mechanical ventilation. Weakness is usually first noted in the legs and ascends to the arms, trunk, head, and neck. Ropper reported that 56% had onset of weakness in the legs, 12% in the arms, and 32% simultaneously in the arms and legs.7,10 Occasionally, there is a descending presentation with onset in the cranial nerves, with subsequent progression to the arms and legs. Mild facial weakness is also often apparent in at least half of the patients during the course of the illness. Ophthalmoparesis and ptosis develop in 5–15% of patients. The bowel and bladder are usually spared, although these may become involved in particularly severe disease states. Muscle stretch reflexes progressively diminish and frequently become unobtainable in keeping with the multifocal demyelination and desynchronization of impulse transmission. Autonomic instability is common in AIDP with hypotension or hypertension and occasionally cardiac arrhythmias. Progressive reversible leukoencephalopathy syndrome (PRES) has also been associated with GBS and may rarely be the initial disease manifestation.39–45
The neuropathy usually progresses over the course of 2–4 weeks. Approximately 50% of patients reach their nadir by 2 weeks, 80% by 3 weeks, and 90% by 4 weeks.7,10 Progression of symptoms and signs for over 8 weeks excludes GBS and suggests the diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP). Subacute onset with progression of the disease over 4–8 weeks has been termed subacute inflammatory demyelinating polyneuropathy. Patients with subacute inflammatory demyelinating polyneuropathy may have a monophasic illness like AIDP or may behave like CIDP and continue to progress unless treated with immunosuppressive or immunomodulating agents.
Approximately 25–30% of patients with AIDP develop ventilatory failure. Because the immune attack of AIDP has an early predilection for the nerve roots. For this reason it is important to follow the strength of neck flexors and extensors and shoulder abductors closely. These muscle groups are innervated by cervical roots close to the phrenic nerve (C3C4), and thus, correlate well with diaphragmatic strength and impending ventilatory failure. Once the disease nadir is reached, there is a plateau phase of several days to weeks followed by gradual recovery over several months. However, 50–85% of patients have some degree of residual deficits as many as 7 years after disease onset, with 5–10% of patients having disabling motor or sensory symptoms as well as severe fatigue.7,10,11,38,46–48
Furthermore, perhaps as many as 5–10% of patients who initially improve will have a relapse within a few days or up to 3 weeks after completion of treatment, and there are cases of CIDP that have begun acutely. It can therefore at times be difficult to ascertain initially if a patient will behave as AIDP or will evolve into CIDP and require long-term immunotherapy. The diagnosis of acute-onset CIDP should be considered when a patient thought to have GBS deteriorates again after 8 weeks from onset or when there are 3 or more relapses.49
The mortality rate in GBS ranges from 2–5%, with patients dying as a result of respiratory distress syndrome, aspiration pneumonia, pulmonary embolism, cardiac arrhythmias, and sepsis related to secondarily acquired infections.7,10,50 Most patients die during the recovery period and not while they are actually getting weaker.50 Risk factors for a poor prognosis (slower and incomplete recovery) include: age greater than 50–60 years, abrupt onset of profound weakness, the need for mechanical ventilation, delay from onset of weakness to treatment, and cumulative distal compound muscle action potential (CMAP) amplitudes less than 10–20% of normal.21,50,52–58
Albuminocytologic dissociation, that is, elevated CSF protein levels accompanied by no or only a few mononuclear cells, is present in over 80% of patients after 2 weeks. However, within the first week of symptoms, CSF protein levels are normal in approximately one-third of patients. When CSF pleocytosis of more than 10 lymphocytes/mm3 (particularly with cell counts greater than 50/mm3) is found, AIDP-like neuropathies related to Lyme disease, recent HIV infection, or sarcoidosis need to be considered. Elevated liver function tests are common and may be attributed to viral hepatitis (A, B, C, and E), Epstein–Barr virus, or cytomegalovirus infection. Some patients develop hyponatremia due to inappropriate anti-diuretic hormone (SIADH) secretion.59,60 Unlike the axonal forms of GBS, antiganglioside antibodies appear to be uncommon in AIDP (Fig. 13-1). However, antibodies directed against moesin, a protein expressed on peripheral nerve myelin, have been found in AIDP associated with recent CMV infection.61 Enhancement of the nerve roots may be appreciated on magnetic resonance imaging of the spine.62
Spectrum of disorders in the Guillain–Barré syndrome and associated antiganglioside antibodies. IgG autoantibodies against GM1 or GD1a are strongly associated with acute motor axonal neuropathy, as well as the more extensive acute motor–sensory axonal neuropathy and the less extensive acute motor-conduction-block neuropathy. IgG anti-GQ1b antibodies, which cross-react with GT1a, are strongly associated with the Miller Fisher syndrome, its incomplete forms (acute ophthalmoparesis [without ataxia] and acute ataxic neuropathy [without ophthalmoplegia]), and its more extensive form, Bickerstaff’s brain-stem encephalitis. Pharyngeal–cervical–brachial weakness is categorized as a localized form of acute motor axonal neuropathy or an extensive form of the Miller Fisher syndrome. Half the patients with pharyngeal–cervical–brachial weakness have IgG anti-GT1a antibodies, which often cross-react with GQ1b. IgG anti-GD1a antibodies have also been detected in a small percentage of patients. The anti-GQ1b antibody syndrome includes the Miller Fisher syndrome, acute ophthalmoparesis, acute ataxic neuropathy, Bickerstaff’s brain-stem encephalitis, and pharyngeal–cervical–brachial weakness. The presence of clinical overlap also indicates that the Miller Fisher syndrome is part of a continuous spectrum with these conditions. Patients who have had the Guillain–Barré syndrome overlapped with the Miller Fisher syndrome or with its related conditions have IgG antibodies against GM1 or GD1 a as well as against GQ1b or GT1a, supporting a link between AMAN and the anti-GQ1b syndrome. CNS, central nervous system. (Reproduced with permission from Yuki N, Hartung H-P. Guillain-Barré syndrome. N Engl J Med. 2012;366:2294–2304.)
Various electrophysiologic criteria for demyelination have been developed to aid in the diagnosis of AIDP (Table 13-3).8 The electrophysiologic features of demyelination include: prolonged distal latencies, slow conduction velocities, temporal dispersion, conduction block, and prolonged F-wave latencies.
Within the first week, motor conduction studies can be normal or show only minor abnormalities. The maximum degree of motor conduction abnormality occurs within 3–8 weeks, with 80–90% of patients with AIDP having abnormalities in at least one of the motor nerve parameters (distal CMAP latency, F-wave latency, conduction velocity, and/or conduction block) within 5 weeks of onset.8,51,52,63–67 F-wave studies are useful because of the early predilection for the proximal nerve segments and spinal roots in AIDP.51,52,63,68 Prolonged or absent F-waves and H-reflexes are found in 80–90% of patients during the course of AIDP.51,52,63,69 They provided greater specificity for a demyelinating neuropathy when prolonged than when they are nonspecifically absent. Albers and colleagues found that prolonged distal latencies and diminished CMAP amplitude were the earliest electrophysiologic abnormalities.63 Within 1 week of symptoms, the mean distal CMAP amplitudes were reduced to approximately 50% of normal and declined further over the next several weeks. Prolonged distal motor latencies and prolonged or absent F-waves were appreciated by the North American Guillain–Barré Syndrome Study Group, reported as the earliest abnormal features—findings that reflect the early predilection for involvement of the proximal spinal roots and distal motor nerve terminals in GBS.51,52 Slowing of conduction velocities, temporal dispersion of the CMAP waveforms, and conduction block become apparent later in the course. The motor conduction abnormalities remain at their nadir for approximately 1 month and then gradually improve over the next several weeks to months, but it may take a year or more for normalization.63 There is no correlation between the nerve conduction velocities (NCVs) or distal motor latencies and clinical severity of the neuropathy, although distal CMAP amplitudes less than 10–20% of normal are associated with a poorer prognosis.51–58
Meulstee and colleagues applied the electrophysiologic criteria for demyelination designed by Albers et al.,63 Barohn et al.,70 and Asbury and Cornblath51,52,71 to 135 patients with AIDP sequentially studied during the Dutch-GBS plasma exchange (PE) and intravenous immunoglobulin (IVIG) trials.72 The sensitivity of the criteria for diagnosing demyelination ranged from 3–36% during the first study (performed at a median of 6 days, range 2–15 days after onset) to 13–46% during the third study (performed at a median of 34 days, range 29–49 days after onset).
Sensory studies in the arms can be affected more severely and earlier than the sural sensory nerve action potentials (SNAPs), resulting in a condition known as “sural sparing,” a helpful diagnostic finding when present.63 Sural sparing is not unique to GBS, however, and can be seen in other non–length-dependent neuropathy syndromes such as sensory neuronopathies. The exact explanation is multifactorial. Perhaps, entrapment sites are more prone to attack, which could account for slowing of the median SNAP across the carpal tunnel. More likely, because AIDP is a multifocal demyelinating disorder rather than a length-dependent process typical of most axonal neuropathies, the median, ulnar, or radial SNAPs may be affected prior to the sural SNAPs.
About 40–60% of patients eventually demonstrate either amplitude reduction or slow conduction velocities, with maximal abnormalities being seen after 4–6 weeks.63,69 Reduced SNAP amplitudes can be the result of secondary axonal degeneration, conduction block, or phase cancellation related to differential demyelination and slowing of the sensory nerve fibers. Sensory conduction velocities can be slow and distal latencies prolonged. By definition, the AMAN variant of GBS is associated with normal sensory conduction studies.
Rarely, some persons may present with what appears to be pure sensory symptoms and signs, but careful evaluation usually reveals some motor nerve conduction abnormalities.73,74 With a pure sensory presentation, other disorders (acute sensory neuronopathy or ganglionopathy) must be ruled out.7
The earliest abnormality on electromyography (EMG) is a reduced recruitment of motor unit action potentials (MUAPs).63 Positive sharp waves and fibrillation potentials may be appreciated 2–4 weeks after onset of weakness as some degree of axon loss is common even in AIDP.75 Myokymic discharges may be seen, especially in facial muscles.
Autonomic instability can be assessed by looking at heart rate variability with deep breathing or Valsalva maneuvers, with about 35% of patients demonstrating an abnormality.76 Sympathetic skin response may be absent, but this has poor sensitivity.
Nerve biopsies are not routinely performed in patients suspected of having GBS. Nonetheless, biopsies have demonstrated endoneurial and perivascular mononuclear cell infiltrate consisting of macrophages and lymphocytes may be seen on light microscopy.7,77–79 There may be an initial preference for the nerve root region, areas where peripheral nerves are commonly entrapped (e.g., carpal and cubital tunnels), and the motor nerve terminals. The earliest pathophysiologic features are often appreciated at the nodes of Ranvier, where there is loosened paranodal myelin and subsequent demyelination of the internodal segments. Monocellular infiltrates may be appreciated in areas of segmental demyelination (Fig. 13-2). Polymorphonuclear cells, in addition to monocytes, may be associated with axonal degeneration in severe cases. During the recovery phase, remyelination is appreciated. Myelin thickness is reduced and the number of internodes is increased compared to normal peripheral nerve.
Nerve fiber from patient with AIDP. Electron micrograph shows that a macrophage (M) has invaded Schwann cell basement membrane and stripped the abaxonal Schwann cell cytoplasm (arrows). (Reproduced with permission from Hughes RA, Cornblath DR. Guillain–Barre syndrome. Lancet. 2005;366(9497):1653–1666.)
Autopsy studies of patients in China who died early in the course of their illness have shed light on the pathology of GBS, including AIDP, AMSAN, and AMAN.80–83 In two patients who died at 7 and 9 days after onset of the neuropathy, autopsies revealed completely demyelinated peripheral nerves accompanied by extensive lymphocytic infiltrate.82 However, in a patient who died only 3 days after symptom onset, the peripheral nerves had only scant inflammatory infiltrate and just a few of the nerves were completely demyelinated. Markers of complement activation were demonstrated on the outermost surface of the Schwann cells, and early vesicular changes in the myelin sheaths, beginning in the outer lamellae, were appreciated on electron microscopy.
A T-cell-mediated process may play a role, given the inflammatory cells apparent in the nerves, markers of T-cell activation (e.g., soluble interleukin-2 receptor and interferon-γ) in the serum, and the resemblance to experimental allergic neuritis.9,84–87 The humoral arm of the immune system has been implicated by the demonstration of ganglioside antibodies in many patients and the clinical improvement following plasmapheresis.85,86 Further, injection of serum from patients with AIDP into nerves of animal models induces complement-dependent demyelination and conduction block.88 Buchwald et al. investigated the effect of serum from 10 patients with GBS on mouse hemidiaphragm using a macro-patch-clamp technique and observed depressed presynaptic transmitter release and, in some cases, activation of postsynaptic channels.89 The neuromuscular blockade was independent of complement, and there was no link to the presence (in six patients) or absence (in four patients) of antibodies to GM1 or GQ1b.
One study revealed that 56 out of 233 (23%) patients with GBS had circulating immunoglobulin G autoantibodies against proliferating, nonmyelinating human Schwann cells.90 Immunofluorescence was localized at the distal tips (leading lamella) of the Schwann cell processes and of nerve-growth cones. Serum immunoreactivity was also observed in teased nerve fiber preparations. The authors speculated that the immune attack may be directed against nonmyelin proteins and epitopes possibly involved in Schwann cell–axon interaction.90
The nature of the epitope is not known but probably is a glycolipid. Molecular similarity between myelin epitope(s) and glycolipids expressed on Campylobacter, Mycoplasma, CMV, and other infectious agents, which precede attacks of AIDP, may be the underlying trigger for the immune attack.11,82 Antibodies directed against these infectious agents may cross-react with specific antigens on the Schwann cell because of this molecular mimicry. These autoantibodies may bind to the Schwann cells and then activate the complement cascade, leading to lysis of myelin sheaths (Fig. 13-3).11,82 Inflammatory cells are subsequently recruited to complete the demyelinating process.
Possible Immune mechanisms in GBS. Panel A shows the immunopathogenesis of AIDP. Although autoantigens have yet to be unequivocally identified, autoantibodies may bind to myelin antigens and activate complement. This is followed by the formation of membrane-attack complex (MAC) on the outer surface of Schwann cells and the initiation of vesicular degeneration. Macrophages subsequently invade myelin and act as scavengers to remove myelin debris. Panel B shows the immunopathogenesis of acute axonal forms of GBS (AMAN and AMSAN). Myelinated axons are divided into four functional regions: the nodes of Ranvier, paranodes, juxtaparanodes, and internodes. Gangliosides GM1 and GD1a are strongly expressed at the nodes of Ranvier, where the voltage-gated sodium (Nav) channels are localized. Contactin-associated protein (Caspr) and voltage-gated potassium (Kv) channels are respectively present at the paranodes and juxtaparanodes. IgG anti-GM1 or anti-GD1a autoantibodies bind to the nodal axolemma, leading to MAC formation. This results in the disappearance of Nav clusters and the detachment of paranodal myelin, which can lead to nerve-conduction failure and muscle weakness. Axonal degeneration may follow at a later stage. Macrophages subsequently invade from the nodes into the periaxonal space, scavenging the injured axons. (Reproduced with permission from Yuki N, Hartung H-P. Guillain-Barré syndrome. N Engl J Med. 2012;366:2294–2304.)
PE53,54,91–93 and IVIG54,94 have been proven effective treatments of AIDP (Table 13-4).95–98 In the North American trial, PE reduced the time necessary to improve one clinical grade, time to walk unaided, time on a ventilator, and the percentages of patients improving after 1 and 6 months compared to the control group.92 The French Plasmapheresis Group confirmed that PE was efficacious in GBS.91 The exact mechanism is unclear, but it is likely that PE removes autoantibodies, immune complexes, complement, or other humoral factors involved in the pathogenesis of AIDP. The standard course of PE is 200–250 mL/kg of patient body weight over 10–14 days. Thus, a 70-kg patient would receive 14,000–17,500 mL (14–17.5 L) total exchange, which can be accomplished by 4–6 alternate day exchanges of 2–4 L each.
|Plasmapheresis Group||Control Group||IVIG Group|
|North American Trial|
|Number of patients||122||123|
|Time to improve one clinical grade (days)||19||40|
|Time to walk unaided (all patients) (days)||53||85|
|Time to walk unaided (ventilator patients) (days)||97||169|
|Time on ventilator (days)||9||23|
|Percentage improved at 1 month||59||39|
|Percentage improved at 6 months||97||87s|
|Number of patients||109||111|
|Percentage of patients on ventilator after study (days)||18||31|
|Time to wean from ventilator (days)||70||111|
|Time to walk unaided (days)||28||45|
|Time in hospital||21||42|
|Dutch IVIG Trial|
|Number of patients||73||74|
|% of patients improving one clinical grade after 4 weeks||34||53|
|Time to improve one clinical grade (days)||41||27|
|Time to clinical Grade 2 (days)||69||55|
|Ventilator dependent by week 2 (%)||42||27|
|Number of multiple complications||16||5|
|PE/Sandoglobulin Trial Group|
|Number of patients||121||130|
|Mean change in clinical grade after 4 weeks||0.9||0.8|
|Time to wean from ventilator (days)||29||26|
|Time to walk unaided (days)||49||51|
|Number of patients unable to walk after 48 weeks||19 (16.7%)||21 (16.5%)|
IVIG has replaced PE in most centers as the treatment of choice of AIDP. IVIG was shown to be at least as effective as PE in nonambulatory adults treated within the first 2 weeks in a prospective trial (Table 13-4).54,94,99 Importantly, there is no added benefit of IVIG following PE, and it certainly makes no sense to give IVIG and then perform PE.54 The dose of IVIG is 2.0 g/kg body weight infused over 2–5 days. Randomized trials are needed to decide the effect of IVIG in children, in adults with mild disease, and in adults who start treatment after more than 2 weeks.95 IVIG may inhibit the binding of ganglioside antibodies to their respective antigens, thereby preventing complement activation and subsequent pathophysiologic effects.100
Treatment with IVIG or PE should begin within the first 7–10 days of symptoms. As the improvement with PE and IVIG is often not immediate (mean time to improvement of one clinical grade in the various controlled, randomized PE and IVIG studies ranged from 6 days to 27 days), there is often an impulse to augment the initial treatment attempt.91,92,94 There is, however, no evidence that PE beyond 250 mL/kg91,101–103 or IVIG greater than 2 g/kg are of any added benefit in patients with AIDP, who have stable deficits that are not improving as quickly as the patient and their physician would like. Further, as noted above, there is no indication for PE followed by IVIG or vice versa. Nonetheless, as many as 10% of patients treated with either PE 91,103 or IVIG 101,102 develop a relapse following initial improvement. In patients who suffer such relapses, we give additional courses of PE or IVIG.
Unlike CIDP, corticosteroids do not appear to be beneficial in the treatment of GBS, and some patients have done worse with steroids. A small study of 25 patients treated with IVIG and intravenous methylprednisolone104 did better than a historical control group treated with IVIG alone.94 However, a much larger British study of 142 patients treated with methylprednisolone or placebo (approximately half the patients in each group were also treated with PE) failed to demonstrate the efficacy of corticosteroids.105 A double-blind, placebo-controlled randomized study of IVIG plus intravenous methylprednisolone compared to IVIG plus placebo in 233 patients with GBS revealed no significant difference between treatment with methylprednisolone and IVIG versus IVIG alone.106 Thus, there is no strong support in the medical literature for supplemental corticosteroid use in patients with GBS.
Children with AIDP have clinical, laboratory, and electrophysiologic findings similar to affected adults.8,79,96,107–111 An antecedent infection within 2 months of the attack is appreciated in approximately 75% of children having AIDP. Most children present with back and extremity pain. Generalized weakness, ventilatory failure, sensory loss (including sensory ataxia), and autonomic dysfunction can develop. Laboratory evaluation is remarkable for an elevated CSF protein. Sural nerve biopsies in children with GBS demonstrate similar histopathologic abnormalities as those described in adults.79
AXONAL GBS: AMSAN
Feasby and colleagues were the first to detail an axonal variant of GBS in 1986.113 Initially, the existence of an axonal variant was met with early skepticism55,113, however subsequent autopsy studies confirmed that AMSAN is a real entity.80,81 Clinically and often by early electrodiagnostic studies, patients with AMSAN are indistinguishable from those with AIDP.8,11,55,79–81,113–120 Usually, sensory symptoms begin in the hands or feet and later progress. Sensation to all modalities is reduced and areflexia is usually evident. Patients with AMSAN rapidly develop progressive and severe generalized weakness over only a few days, as opposed to progression over a couple of weeks in most patients with AIDP. Ophthalmoplegia, dysphagia, and ventilatory muscle weakness can occur. Dysautonomia including labile blood pressure and cardiac arrhythmias may complicate AMSAN as well. Recovery of strength and function is slow and often incomplete compared to AIDP.118 Only a few children have been reported with AMSAN, and there is some suggestion that the prognosis is better than in adults.113,120
Albuminocytologic dissociation of the CSF protein is usually seen. Evidence of a recent infection with C. jejuni and antibodies directed against nerve gangliosides, particularly GM1 antibodies, are demonstrated in many patients with AMSAN.11,81,121–123 NCS reveal markedly diminished amplitudes or absent CMAPs and SNAPs within 7–10 days of onset.8,51,113,115–119,124,125 As discussed in the AIDP section, low-amplitude CMAPs are one of the earliest electrophysiologic abnormalities noted in AIDP; thus, low-amplitude CMAPs do not necessarily imply axonal degeneration. Distal conduction block with or without demyelination also leads to low-amplitude distal CMAPs.55,114 Initially, it is often impossible to distinguish AIDP from AMSAN by nerve conduction studies; however, serial nerve conduction studies may be helpful.114 Most patients with AIDP will eventually develop other features of demyelination (e.g., significantly prolonged distal latencies and F-wave latencies, slow CVs, more proximal conduction block, or temporal dispersion). The distal latencies of the CMAPs and the NCVs, when obtainable, should be normal or only mildly affected in AMSAN. Needle EMG demonstrates a markedly abnormal reduction in recruitment. Several weeks after the presentation of major motor weakness, abundant fibrillation potentials and positive sharp waves can be detected in most muscles, especially those located in the distal regions of the limbs.122,123,126