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Recovery patterns and long term prognosis for axonal Guillain–Barré syndrome
http://www.100md.com 《神经病学神经外科学杂志》
     1 Department of Neurology, Chiba University Graduate School of Medicine, Chiba, Japan

    2 Department of Neurology, Matsudo Municipal Hospital, Matsudo, Japan

    Correspondence to:

    Dr Akiyuki Hiraga

    Department of Neurology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan; hiragaa@mail3.alpha-net.ne.jp

    ABSTRACT

    Background: Little is known about the long term prognosis for patients the severe acute motor axonal neuropathy (AMAN) form of Guillain–Barré syndrome (GBS), unlike those with acute inflammatory demyelinating neuropathy (AIDP).

    Objective: To clarify the long term prognosis for patients with AMAN.

    Methods: Clinical recovery and outcome in 97 consecutive GBS patients were reviewed.

    Results: Electrodiagnostic criteria showed that 44 patients (45%) had AMAN, 33 (34%) had AIDP, and 20 (21%) were unclassified. Most of the severely affected patients had

    Conclusions: AMAN electrodiagnosis is not always a marker of poor recovery. Almost all the severe AMAN patients who had slow recoveries over the first six months could eventually walk independently, although some required several years.

    Abbreviations: AIDP, acute inflammatory demyelinating polyneuropathy; AMAN, acute motor axonal neuropathy; GBS, Guillain–Barré syndrome

    Keywords: Guillain-Barré syndrome; acute inflammatory demyelinating polyneuropathy; acute motor axonal neuropathy; prognosis

    On the basis of pathological and electrophysiological observations, Guillain–Barré syndrome (GBS) has been regarded as a type of demyelinating neuropathy. In 1986, Feasby et al identified an axonal type of GBS coupled with poor recovery characterised by severe Wallerian-like degeneration in the peripheral nerves at necropsy.1 In the 1990s, a pure motor axonal form of GBS, designated acute motor axonal neuropathy (AMAN), was recognised in northern China2–4 and later reported in other countries.5,6,7,8,9,10,11,12 Based on the electrophysiological and pathological findings, GBS is currently divided into demyelinating and axonal forms: acute inflammatory demyelinating polyneuropathy (AIDP) and AMAN.1,2,3,4,5,6,7,8,9,10,11,12 Axonal GBS is usually characterised by electrophysiological and pathological evidence of axonal degeneration of the motor nerves together with functional conduction failure or other pathophysiology, and a possible association with anti-ganglioside antibodies, Campylobacter jejuni infection, or both.10 Electrophysiological evidence of axonal degeneration is thought to be an indicator of poor prognosis,8,13–18 but AMAN patients often show rapid recovery.9,19–21 Moreover, little is known about the long term outcome in these patients. We investigated differences in recovery patterns of AIDP and AMAN patients, and clarified the long term prognosis for severely disabled AMAN patients.

    METHODS

    Patients

    We studied a series of 97 consecutive GBS patients seen at Chiba University Hospital or Matsudo Municipal Hospital between 1992 and 2002. All fulfilled the clinical criteria for GBS.22 Disabilities were evaluated on the Hughes functional grading scale (grade 6, dead; grade 5, requires assisted respiration; grade 4, bed bound; grade 3, able to walk 5 m with aid; grade 2, ambulates independently; grade 1, minimal signs and symptoms, able to run; grade 0, normal). Patients were followed for more than six months from neurological onset. Rapid recovery was defined as an improvement by two or more Hughes grades within four weeks after onset, and slow recovery as the inability to walk independently (grade 3 or more) six months after neurological onset.

    Electrophysiology

    Nerve conduction studies were undertaken using conventional procedures. Motor conduction studies were made on the median, ulnar, tibial, and peroneal nerves, and sensory conduction studies on the median, ulnar, and sural nerves. Patients were classified as having AMAN or AIDP on the basis of the electrodiagnostic criteria of Ho et al.4 When patients had one of the following findings in two or more nerves during the first two weeks of illness, they were classified as having AIDP:

    conduction velocity <90% of lower limit of normal if amplitude is >50% of the lower limit of normal; <85% if amplitude is <50% of lower limit of normal;

    distal latency >110% of upper limit of normal if amplitude is normal; >120% of upper limit of normal, if the amplitude is less than lower limit of normal;

    evidence of unequivocal temporal dispersion;

    F response latency >120% of normal.

    When patients had no evidence of demyelination as defined for AIDP, and had a decrease in CMAP to <80% of lower limit of normal in two or more nerves, they were classified as having AMAN.

    Statistical analysis

    Differences in proportions were tested with the 2 or Fisher’s exact test, and differences in medians with the Mann–Whitney U test. A probability (p) value of <0.05 was considered significant. Kaplan–Meier curves were used to analyse the time taken to reach Hughes grade 2 (independent locomotion).

    RESULTS

    Patients

    The 97 patients were grouped as having AMAN (n = 44; 45%), AIDP (n = 33; 34%), or unclassified (n = 20; 21%). Clinical features of the patients with AMAN or AIDP are summarised in table 1. AMAN patients more often had preceding gastroenteritis than AIDP patients, but age, sex, and the frequency of immune treatments did not differ between the two groups, nor was there a significant difference in the median Hughes grade at nadir between the groups.

    Table 1 Clinical features

    "Unclassified" patients had milder conduction abnormalities which did not meet the criteria of AIDP and AMAN. Clinical severity in these patients was also milder (mean Hughes grade, 3.1). We think that these cases represent milder phenotypes of each subgroup of GBS.

    Clinical recovery of AMAN and AIDP patients

    Table 2 shows clinical recovery in the AMAN and AIDP groups and its relation to treatment. The AMAN group had higher percentages of patients with slow recovery (unable to walk independently at six months) and of those with rapid recovery (improvement by two Hughes grades or more during the first four weeks), but the differences were not significant. All the patients who had rapid or slow recovery had

    Table 2 Recovery measures and treatment methods

    Figure 1 Histograms showing periods until an improvement of one Hughes grade from onset. The acute motor axonal neuropathy group (AMAN) (black bars; n = 35) had two subgroups of patients who improved by one grade within four weeks or over a period of months. The acute inflammatory demyelinating polyneuropathy group (AIDP) had a relatively uniform pattern (white bars; n = 22).

    Figure 2 Kaplan–Meier curves showing the probability that patients would not recover independent locomotion (Hughes grade 2). AIDP, acute inflammatory demyelinating polyneuropathy; AMAN, acute motor axonal neuropathy.

    Patients unable to walk six months after onset

    Of all the GBS patients, eight (two AIDP and six AMAN) were unable to walk (Hughes grade 3 or more) six months after onset. The clinical profiles of these eight patients are shown in table 3. All had

    Table 3 Patients unable to walk independently at six months after onset

    Figure 3 Milestones of recovery for Guillain-Barré syndrome patients unable to walk independently at six months after onset. Grey bars, acute motor axonal neuropathy (patients 1–6); black bars, acute inflammatory demyelinating polyneuropathy (patients 7 and 8).

    DISCUSSION

    Our results confirm that two patterns of clinical recovery are found in AMAN patients, in contrast to a relatively uniform recovery in AIDP patients; they showed that the long term prognosis of patients with severe AMAN was quite good, with most of the severely disabled patients being able to walk independently within a few years.

    Necropsy studies of AMAN patients have detected extensive Wallerian-like degeneration in the ventral roots.3 Although some AMAN patients experience slow, incomplete recovery, many recover well.9,19–21 In a report on the patterns of recovery of 32 AMAN and eight AIDP patients in northern China,19 some of the AMAN group had rapid clinical recoveries, and the recovery times of AIDP and AMAN patients were similar. In our previous study of 41 GBS cases, the anti-GM1 positive patients—most of whom had AMAN—had two patterns of clinical recovery: rapid and prolonged.9 AMAN patients in our present study had a two phase recovery pattern similar to that of the former anti-GM1 positive patients. This good potential for recovery from AMAN suggests that extensive axonal degeneration is not always the underlying pathophysiology. The rapid recovery of AMAN patients may be explained by early resolution of physiological conduction failure at the nodes of Ranvier in the motor fibres19,23,24 or by collateral sprouting of surviving axons, as proposed previously.20

    The functional outcome of GBS in large series has been well documented.11,14,16,25–27 In the MGH retrospective series, 6% needed canes, crutches, or braces to walk at six to nine months, 3% remained wheelchair bound at two to three years, and 5% had died at 15 to 210 days after disease onset.25 In south-east England in 1983–1984, 8% of 87 surviving GBS patients still had a disability grade of 3 or 4 one year after onset.14 At that time, 13% of the GBS patients in the study had died,14 and 20% of 79 patients in a 1993–1994 survey.26 In a recent large prospective Italian study, 15% of 108 surviving GBS patients had a disability grade of 3 or more two years after onset.11 In a Dutch study, 24% of 147 GBS patients had a disability grade of 2 or more at six months,16 and 11% could not walk independently 2.5–6.5 years after onset.27 Immune treatment is strongly associated with the prognosis for GBS patients; thus it is hard to compare results of our present study with studies done before the introduction of intravenous immunoglobulin or plasmapheresis.

    The frequency of AMAN varies according to country, from only 7% of GBS patients studied in England28 and 3% in a multicentre study done in 11 Western countries29 to 65% in a study in northern China.4 The low percentages of patients with AMAN in Western countries may affect study results. Previous studies of the long term prognosis for GBS patients in Western countries focused on AIDP, and little is known about the long term outcome for patients with AMAN. Of 32 AMAN and eight AIDP patients in northern China,19 more than 90% of the AMAN patients and all the AIDP patients could walk five metres with a walker or support. The Chinese AMAN patients, however, were markedly younger (median age 10 years) than the AIDP patients (median age 42 years). A comparison of the prognosis for AMAN and AIDP patients is therefore difficult. In the multicentre study of 369 GBS patients in 11 Western countries,29 axonal GBS accounted for 3% (10 patients); 10% of those with the axonal form and 17% with the demyelinating form could not walk or were dead 48 weeks after onset. The numbers of patients unable to walk and those who died did not differ significantly for the axonal and demyelinating forms. AIDP can be accompanied by secondary axonal degeneration in severe cases, and AMAN could be associated with functional conduction block as well as axonal loss.24 These might be the reasons why the long term prognosis of AMAN and AIDP is almost the same.

    In our study, 8% of the 97 patients with GBS (six AMAN and two AIDP) could not walk independently at six months after onset. In the AMAN group, four of the six could walk independently one year after onset, one could walk independently 28 months after onset, and the remaining patient could walk 57 months after onset. Generally, it is believed that no further recovery can be expected two to three years after GBS,30 but follow up has mainly been limited to six months or one year in most previous studies, which may be the reason for the overly pessimistic outlook for long term recovery from severe GBS.31 In our study, two AMAN patients who had slow recoveries could walk independently 28 and 57 months after onset. In addition, in the Dutch study, 21% of the GBS patients continued to improve after 2.5 to 6.5 years.27 The mechanism of improvement in patients with severe GBS several years after onset is not clear, but axonal regeneration along the course of the nerve may account for it.

    Conclusions

    Most of the severely disabled AMAN patients who are unable to walk six months after onset, may still show improvement over a period of years and may ultimately be able to walk independently. Neurologists should conduct long term follow up studies of severe AMAN patients and recommend long term rehabilitation.

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