NDIA Accountability Project

This project is in DRAFT

Research – Guillain Barre Syndrome

‹ PrevPage 1 of 10 · Source p. 1Next ›

Research – Guillain Barre Syndrome

Research on Guillain Barre Syndrome & the different variants including Acute Motor Sensory Axonal Neuropathy (AMSAN)

Brief

Detail on recovery including timeframes of each variant. For example, a diagnosis of what period of time would be reasonable to consider if the diagnosis is going to be or likely to be permanent. Stats on cases where permanency is established.

Date 05/08/2021
Requester(s) Jenni G[s47F - personal privacy](/foi-library/releases/759e22e37354-foi-24-25-0593-decision-document/release-materials/material-001__s47f-personal-privacy/)
Researcher Jane Ss47F - personal privacy
Cleared N/A

Please note:

The research and literature reviews collated by our TAB Research Team are not to be shared external to the Branch. These are for internal TAB use only and are intended to assist our advisors with their reasonable and necessary decision-making. Delegates have access to a wide variety of comprehensive guidance material. If Delegates require further information on access or planning matters they are to call the TAPS line for advice. The Research Team are unable to ensure that the information listed below provides an accurate & up-to-date snapshot of these matters.

The contents of this document are OFFICIAL

Contents

  • Summary
  • Overview
  • Variants and Subtypes
  • Clinical Course
  • Prognosis
  • Long Term Outcomes
  • References

Summary

OFFICIAL Research – Guillain Barre Syndrome Page 1 of 10 Page 1 of 10

  • Guillain–Barré syndrome has many variants and can be placed into subtypes using electrophysiological/nerve conduction studies. However, the literature investigating recovery and long term outcomes present results for the condition as a whole rather than within these classifications.
  • The prognosis of GBS is generally considered favourable with most recovery occurring in the first 12 months.
  • Patients have been shown to experience a range of long-term residual problems, including incomplete recovery of motor and sensory function, as well as fatigue, pain and psychological distress.
    • These poor outcomes have been shown to be present up to 10 years after the acute phase.
    • One literature review found that GBS causes severe persistent disability in 14% of patients at 1 year.
    • Other studies have shown that improvements can occur 2-5 years after diagnosis, however, this does not mean they have completely recovered.

Overview

Guillain–Barré syndrome (GBS) is an inflammatory disease of the peripheral nervous system (PNS) and is the most common cause of acute flaccid paralysis, with an annual global incidence of approximately 1-2 per 100,000 person-years [1]. GBS occurs more frequently in males than in females and the incidence increases with age, although all age groups can be affected [1]. Patients with GBS typically present with weakness and sensory signs in the legs that progress to the arms and cranial muscles. Clinical presentation of the disease is heterogeneous and the diagnosis of GBS is based on the patient history and neurological, electrophysiological and cerebrospinal fluid (CSF) examinations. In lower resource countries where Electrophysiological studies are not available, the Brighton Criteria is utilised to make a diagnosis. The table below is used to rank level of severity [2].

OFFICIAL Research – Guillain Barre Syndrome Page 2 of 10

Brighton criteria for GBS

  • present; - absent; +/−, present or absent; CSF, cerebrospinal fluid; GBS, Guillain-Barré syndrome; NCS, nerve conduction study
Diagnostic criteria Level of diagnostic certainty
Absence of alternative diagnosis for weakness Level 1 Level 2 Level 3 Level 4
Diminished or absent deep tendon reflex in weak limbs + + + +/−
Monophasic course and time between onset and nadir, 12 hours to 28 days + + + +/−
Bilateral and flaccid weakness of limbs + + + +/−
CSF cell count <50 cells/microL + + - +/−
CSF protein concentration > normal value + +/− - +/−
NCS findings consistent with one of the subtypes of GBS + +/− - +/−

Variants and Subtypes

Clinical variants of GBS exist, with some patients having a distinct and persistent clinical variant of GBS that does not progress to the classic pattern of sensory loss and weakness [3]. These variants include [3]:

  • Classic Sensorimotor GBS:
    • Rapidly progressive symmetrical weakness and sensory signs with absent or reduced tendon reflexes, usually reaching nadir within 2 weeks
    • 30-85% of cases
  • Pure motor
    • Motor weakness without sensory signs
    • 5-70% of cases
  • Paraparetic
    • Paresis restricted to the legs
    • 5-10%
  • Pharyngeal–cervical– brachial
    • Bilateral facial weakness, paraesthesias and reduced reflexes
  • Bilateral facial palsy with paraesthesias
    • Bilateral facial weakness, paraesthesias and reduced reflexes
    • <5%
  • Pure Sensory

Official

  • Acute or subacute sensory neuropathy without other deficits
  • <1% • Miller Fisher syndrome
    • Ophthalmoplegia, ataxia and areflexia. Incomplete forms with isolated ataxia (acute ataxic neuropathy) or ophthalmoplegia (acute ophthalmoplegia) can occur. Overlaps with classical sensorimotor GBS in an estimated 15% of patients.
    • 5-25% of cases
    • Weakness limited to the cranial nerves (bilateral facial palsy with paraesthesias) • Bickerstaff brainstem encephalitis
    • Ophthalmoplegia, ataxia, areflexia, pyramidal tract signs and impaired consciousness, often overlapping with sensorimotor GBS.
    • <5% of cases In general, GBS variants are rarely ‘pure’ and often overlap in part with the classic syndrome or show features that are typical of other variant forms. Electrophysiological/nerve conduction studies provide evidence of PNS dysfunction and can distinguish between the subtypes of GBS, however, these tests are not required to make a clinical diagnosis of GBS and should not delay treatment [3, 4]. Subtypes include: • Acute inflammatory demyelinating polyradiculoneuropathy (AIDP)
    • Characterized by progressive areflexic (muscles don’t respond to stimuli) weakness and mild sensory changes. Sensory symptoms often precede motor weakness. AIDP is the most common form of GBS in North America and Europe • Acute motor axonal neuropathy (AMAN)
    • Key clinical features of pure motor weakness, areflexia, absence of sensory symptoms, and lack of neurophysiologic evidence of demyelination. • Acute motor sensory axonal neuropathy (AMSAN) [5]
    • Characterised by acute onset of distal weakness, loss of deep tendon reflexes and sensory symptoms
    • Electrophysiological studies show mildly reduced nerve conduction velocities combined with a marked reduction of muscle action and sensory nerve action potentials.

Clinical Course

Disease progression can be rapid, and most patients with GBS reach their maximum disability within 2 weeks. About 20% of patients with GBS develop respiratory failure and require mechanical ventilation. Cardiac arrhythmias and blood pressure instability can occur owing to involvement of the autonomic nervous system [6]. This involvement of the

Prognosis

The prognosis of GBS is generally considered favourable. Despite the demonstrated efficacy of plasma exchange (PE) and intravenous immunoglobulins (IVIg), GBS however

Document 9

OFFICIAL

autonomic nervous system contributes to mortality, which is estimated at 3–10% for patients with GBS even with the best medical care available [6, 7]. After the initial progressive phase, patients with GBS reach a plateau phase that can last from days to weeks or months, after which they start to recover, and 60–80% of patients with GBS are able to walk independently 6 months after disease onset, with or without treatment [8, 9]. GBS is a monophasic illness (a disorder that causes only one episode of inflammation in the central nervous system), although some patients can deteriorate after first stabilizing or improving on therapy — a phenomenon that is referred to as a treatment-related fluctuation (TRF). Relapses of GBS can occur in 2–5% of patients [8, 10, 11]. Willison, Jacobs [6] have developed a figure (below) which describes the clinical course of the disease.

[Image not converted to Markdown – check the source PDF page for the actual content]

OFFICIAL

Research – Guillain Barre Syndrome Page 5 of 10

Page 5 of 10

Long Term Outcomes

The long-term follow-up system of patients with GBS is not well established worldwide [15]. Many follow up studies only review patients 12 months after the acute state. Nonetheless, long-term function has been shown to be compromised in a significant proportion of subjects. Clinical improvement is usually most extensive in the first year after disease onset and can continue for >5 years [3, 15, 16].

Patients with GBS have been shown to experience a range of long-term residual problems, including incomplete recovery of motor and sensory function, as well as fatigue, pain and psychological distress [16-18].

A high quality literature review by Rajabally and Uncini [12] was conducted to determine outcomes and predictors in adequately treated (with PE and IVIg), adult-onset GBS. The table below shows the results from this review. Key findings include that GBS cause’s severe

Research – Guillain Barre Syndrome

persistent disability in 14% of patients at 1 year and loss of full strength, persistent pain and need for professional change occurs in about 40% of patients.

Study Design Outcome 1 (ability to walk with aid at 4 weeks) Outcome 2 (ability to walk unaided at 4 weeks) Outcome 3 (need for ventilatory support at 4 weeks) Outcome 4 (ability to walk unaided at 6 months) Outcome 5 (relapse at 1 year) Outcome 6 (recovery of full motor strength at 1 year) Outcome 7 (ability to walk unaided at 1 year or later) Outcome 8 (persistence of severe motor sequelae at 1 year or later) Outcome 9 (need to change employment due to GBS) Outcome 10 (death within 1 year of diagnosis)
Greenwood et al., 198411 Therapeutic (PE), controlled NA NA 2/14 NA 1/14 4/14 NA 1/14 NA 2/14
Osterman et al., 198412 Therapeutic (PE), controlled 12/18 7/18 4/18 NA 1/18 16/18 NA 1/18 NA 1/18
The GBS Study Group, 198514 Therapeutic (PE), controlled NA NA 26/122 100/122 2/122 NA NA 22/122 NA 3/122
French Cooperative Group, 198715 Therapeutic (PE), controlled 13/109 15/109 12/109 NA 6/109 70/109 NA 11/109 NA 7/109
Färkkilä et al., 198717 Therapeutic (PE), controlled NA NA NA NA 12/13 NA 0/13 NA 2/13
Van der Meché Schmitz, 199218 Therapeutic (PE vs IVlg), controlled NA NA NA NA NA NA NA NA 3/150
French Cooperative Group, 199719 Therapeutic (PE), controlled and ‘dose-ranging’ 6/45† 13/45† 0/45** NA 14/361‡ 210/361‡ NA 41/361‡ NA 14/361‡
PE/Sandoglobulin Trial, 199710 Therapeutic PE versus IVlg versus PE + IVlg NA NA NA NA NA NA NA 57/365* † NA 19/379
van Koningsveld et al., 200411 Therapeutic IVlg + PE versus IVlg + placebo NA NA NA NA NA NA 184/225§ 41/225† † NA 10/225§
Bernsen et al., 200214 Therapeutic (PE vs IVlg), controlled NA NA NA NA NA 108/122 14/122 31/82 NA

The first long-term study of residual health status was published in 1997 analysing a cohort of 123 GBS patients followed up 3-6 years after their illness [19]. The authors found residual altered psychosocial function in all GBS patient groups whether or not they had persistent residual symptoms. However, the ‘physical sickness impact profile’ score correlated with the GBS functional score [19].

The same group later showed long-term reduction in health-related quality of life despite good physical recovery [20]. They also studied the effects on private life of GBS patients 3-6 years after the illness, with 31% showing moderate to serious physical residual symptoms after a functional assessment [21]. Also, and importantly, employment change was needed

OFFICIAL

in 38% of cases and leisure activities had altered in 52% after the illness. However, over 20% of patients still noticed improvement 2.5-6.5 years after onset [21]. Long term outcomes in patients requiring mechanical ventilation has shown that 21% do not regain independent ambulation [22]. This group has the highest mortality rate – which is 20%. A 3 year follow up study to investigate the outcomes of 82 patients found that [23]:

  • Poor functional outcome was found in 39% of patients at year 1 and 30% at year 3.
  • Paresthesias/dysesthesias were detected in 60% of patients after 1 year and 43% after 3 years.
  • Musculoskeletal pain was present in 40% of patients at year 1 and 33% at year 3.
  • Significant fatigue after 1 year was found in 21% of subjects and after 3 years in 7%.

The longest study to date (up to 10 years) included a small sample of 29 patients. Results showed that at 10 years, the facial paralysis found in 5 participants at 2 years was still present, 11 participants (38%) experienced paresthesia, 6 (21%) had limitations in their arms, and 15 (52%) had limitations in walking [16].

OFFICIAL

Research – Guillain Barre Syndrome Page 8 of 10 Page 8 of 10

References

  1. Sejvar JJ, Baughman AL, Wise M, Morgan OW. Population Incidence of Guillain-Barré Syndrome: A Systematic Review and Meta-Analysis. Neuroepidemiology [Internet]. 2011; 36(2):[123-33 pp.]. Available from: https://www.karger.com/DOI/10.1159/000324710.

  2. Ghazanfar H, Qazi R, Ghazanfar A, Iftekhar S. Significance of Brighton Criteria in the Early Diagnosis and Management of Guillain-Barré Syndrome. Cureus [Internet]. 2020; 12(5):[e8318-e pp.]. Available from: https://pubmed.ncbi.nlm.nih.gov/32607301.

  3. Leonhard SE, Mandarakas MR, Gondim FAA, Bateman K, Ferreira MLB, Cornblath DR, et al. Diagnosis and management of Guillain–Barré syndrome in ten steps. Nature Reviews Neurology [Internet]. 2019; 15(11):[671-83 pp.]. Available from: https://doi.org/10.1038/s41582-019-0250-9.

  4. Hadden RDM, Cornblath DR, Hughes RAC, Zielasek J, Hartung HP, Toyka KV, et al. Electrophysiological classification of guillain-barré syndrome: Clinical associations and outcome. Annals of Neurology [Internet]. 1998; 44(5):[780-8 pp.]. Available from: https://doi.org/10.1002/ana.410440512.

  5. Rostásy KM, Huppke P, Beckers B, Brockmann K, Degenhardt V, Wesche B, et al. Acute motor and sensory axonal neuropathy (AMSAN) in a 15-year-old boy presenting with severe pain and distal muscle weakness. Neuropediatrics [Internet]. 2005 Aug; 36(4):[260-4 pp.].

  6. Willison HJ, Jacobs BC, van Doorn PA. Guillain-Barré syndrome. The Lancet [Internet]. 2016; 388(10045):[717-27 pp.]. Available from: https://www.sciencedirect.com/science/article/pii/S0140673616003391.

  7. van den Berg B, Bunschoten C, van Doorn PA, Jacobs BC. Mortality in Guillain-Barré syndrome. Neurology [Internet]. 2013; 80(18):[1650 p.]. Available from: http://n.neurology.org/content/80/18/1650.abstract.

  8. Fokke C, van den Berg B, Drenthen J, Walgaard C, van Doorn PA, Jacobs BC. Diagnosis of Guillain-Barré syndrome and validation of Brighton criteria. Brain [Internet]. 2014; 137(1):[33-43 pp.]. Available from: https://doi.org/10.1093/brain/awt285.

  9. Doets AY, Verboon C, van den Berg B, Harbo T, Cornblath DR, Willison HJ, et al. Regional variation of Guillain-Barré syndrome. Brain [Internet]. 2018; 141(10):[2866-77 pp.]. Available from: https://doi.org/10.1093/brain/awy232.

  10. Ruts L, Drenthen J, Jacobs BC, van Doorn PA. Distinguishing acute-onset CIDP from fluctuating Guillain-Barré syndrome. Neurology [Internet]. 2010; 74(21):[1680 p.]. Available from: http://n.neurology.org/content/74/21/1680.abstract.

  11. Kleyweg RP, van der Meché FG. Treatment related fluctuations in Guillain-Barré syndrome after high-dose immunoglobulins or plasma-exchange. Journal of Neurology, Neurosurgery &amp; Psychiatry [Internet]. 1991; 54(11):[957 p.]. Available from: http://jnnp.bmj.com/content/54/11/957.abstract.

  12. Rajabally YA, Uncini A. Outcome and its predictors in Guillain–Barré syndrome. Journal of Neurology, Neurosurgery &amp; Psychiatry [Internet]. 2012; 83(7):[711 p.]. Available from: http://jnnp.bmj.com/content/83/7/711.abstract.

  13. van Koningsveld R, Steyerberg EW, Hughes RAC, Swan AV, van Doorn PA, Jacobs BC. A clinical prognostic scoring system for Guillain-Barré syndrome. The Lancet Neurology [Internet].

OFFICIAL

2007 2007/07/01/; 6(7):[589-94 pp.]. Available from: https://www.sciencedirect.com/science/article/pii/S1474442207701308.

References

  1. Walgaard C, Lingsma HF, Ruts L, Drenthen J, van Koningsveld R, Garssen MJP, et al. Prediction of respiratory insufficiency in Guillain-Barré syndrome. Annals of Neurology [Internet]. 2010; 67(6):[781-7 pp.]. Available from: https://doi.org/10.1002/ana.21976.

  2. Wang Y, Lang W, Zhang Y, Ma X, Zhou C, Zhang H-L. Long-term prognosis of Guillain-Barré syndrome not determined by treatment options? Oncotarget [Internet]. 2017; 8(45):[79991-80001 pp.]. Available from: https://pubmed.ncbi.nlm.nih.gov/29108381.

  3. Forsberg A, Press R, Holmqvist LW. Residual disability 10 years after falling ill in Guillain–Barré syndrome: A prospective follow-up study. Journal of the Neurological Sciences [Internet]. 2012; 317(1):[74-9 pp.]. Available from: https://www.sciencedirect.com/science/article/pii/S0022510X12001098.

  4. Soysal A, Aysal F, Calıskan B, Dogan Ak P, Mutluay B, Sakallı N, et al. Clinico-electrophysiological findings and prognosis of Guillain-Barré syndrome – 10 years’ experience. Acta Neurologica Scandinavica [Internet]. 2011; 123(3):[181-6 pp.]. Available from: https://doi.org/10.1111/j.1600-0404.2010.01366.x.

  5. Bersano A, Carpo M, Allaria S, Franciotta D, Citterio A, Nobile-Orazio E. Long term disability and social status change after Guillain–Barré syndrome. Journal of Neurology [Internet]. 2006; 253(2):[214-8 pp.]. Available from: https://doi.org/10.1007/s00415-005-0958-x.

  6. Bernsen RA, Jacobs HM, de Jager AE, van der Meché FG. Residual health status after Guillain-Barré syndrome. Journal of Neurology, Neurosurgery &amp; Psychiatry [Internet]. 1997; 62(6):[637 p.]. Available from: http://jnnp.bmj.com/content/62/6/637.abstract.

  7. Bernsen RAJAM, de Jager AEJ, Schmitz PIM, van der Meché FGA. Residual physical outcome and daily living 3 to 6 years after Guillain-Barré syndrome. Neurology [Internet]. 1999; 53(2):[409 p.]. Available from: http://n.neurology.org/content/53/2/409.abstract.

  8. Bernsen RAJAM, de Jager AEJ, Schmitz PIM, van der Meché FGA. Long-term impact on work and private life after Guillain–Barré syndrome. Journal of the Neurological Sciences [Internet]. 2002; 201(1):[13-7 pp.]. Available from: https://www.sciencedirect.com/science/article/pii/S0022510X02001582.

  9. Fletcher DD, Lawn ND, Wolter TD, Wijdicks EFM. Long-term outcome in patients with Guillain–Barré syndrome requiring mechanical ventilation. Neurology [Internet]. 2000; 54(12):[2311 p.]. Available from: http://n.neurology.org/content/54/12/2311.abstract.

  10. Martic V, Bozovic I, Berisavac I, Basta I, Peric S, Babic M, et al. Three-Year Follow-Up Study in Patients with Guillain-Barré Syndrome. Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques [Internet]. 2018; 45(3):[269-74 pp.]. Available from: https://www.cambridge.org/core/article/threeyear-followup-study-in-patients-with-guillainbarre-syndrome/F9B56E8172040A3A0D8E79DB9B4D9902.

OFFICIAL

Research – Guillain Barre Syndrome Page 10 of 10

                                                  Page 10 of 10