8/3/2019 nrneurol.2011.93

1/2362 | JULY 2011 | VOLUME 7 www.nature.com/nrneurol

NEWS & VIEWS

forms of neuropathic pain arose from animbalance between nociceptive and antinociceptive fiber activity and, togetherwith his colleagues at Johns Hopkins, hedemonstrated the role of Schwann celland Cfiber interaction in the initiation ofneuropathic pain.6,7

Jacks research was always intertwinedwith teaching and promoting the careerdevelopment of his mentees. He alwaystook pride in the accomplishments of histrainees and did whatever he could toprovide the support they needed early in

their independent careers. His support ofcareer development of junior membersof the profession did not stop with his owntrainees, but extended to others as well. Thisclassic quote from Goethe sums up Jacksapproach to this domain: who is the happiest of men? He who values the merits ofothers, and in their pleasure takes joy, evenas though twere his own.

Jack was the Editorin Chief ofNatureReviews Neurology (originallyNature ClinicalPractice Neurology) from its launch in 2005,and continued to serve on its Advisory Board

following editorial restructuring in June2010. Jack was instrumental in the launchof the journal, helping the editorial teamto appoint a firstclass Advisory Board andto develop commissioning ideas. He regularly contributed insightful and entertaining Editorials, drawing on his experiencesas both a clinician and a patient.810 He wasalso an excellent ambassador for the journal,and had a strong vision for the direction itshould take, in terms of both content anddesign. He was always extremely supportive of the editorial team, providing valuable

advice when needed but also allowing themthe freedom to develop their own ideas.Jacks input has undoubtedly been vital tothe success of the journal, and he will begreatly missed.

Jacks loss is tremendous to his family,to the academic community, and to hispatients and colleagues. He will always beremembered for his warm smile, great senseof humor, leadership in academic medicine,strong advocacy for junior members of theprofession, and many original contributionsto neuroscience and neurology.

Johns Hopkins University, The John G. Rangos

Sr Building, 855 N. Wolfe Street, Neurology

248, Baltimore, MD, 21205, USA (A. Hke).

University of Glasgow College of Medical,

Veterinary and Life Sciences, Glasgow

Biomedical Research Centre, Room B330,

120 University Place, Glasgow G12 8TA, UK

(H. J. Willison).

Correspondence to: A. Hke

ahoke@jhmi.edu

Competing interests

The authors declare no competing interests.

1. Stoll, G., Trapp, B. D. & Griffin, J. W.

Macrophage function during Wallerian

degeneration of rat optic nerve: clearance of

degenerating myelin and Ia expression.

J. Neurosci. 9, 23272335 (1989).

2. Farah, M. H. et al. Reduced BACE1 activity

enhances clearance of myelin debris and

regeneration of axons in the injured peripheral

nervous system.J. Neurosci. 31, 57445754

(2011).

3. Hafer-Macko, C. et al. Acute motor axonal

neuropathy: an antibody-mediated attack

on axolemma.Ann. Neurol. 40, 635644

(1996).

4. Hafer-Macko, C. E. et al. Immune attack on the

Schwann cell surface in acute inflammatory

demyelinating polyneuropathy.Ann. Neurol. 39,

625635 (1996).

5. Ho, T. W., McKhann, G. M. & Griffin, J. W.

Human autoimmune neuropathies.Annu. Rev.

Neurosci.21, 187226 (1998).6. Wu, G. et al. Early onset of spontaneous activity

in uninjured C-fiber nociceptors after injury to

neighboring nerve fibers.J. Neurosci. 21, RC140

(2001).

7. Wu, G. et al. Degeneration of myelinated

efferent fibers induces spontaneous activity in

uninjured C-fiber afferents.J. Neurosci. 22,

77467753 (2002).

8. Griffin, J. W. Teaching and learning empathy.

Nat. Clin. Pract. Neurol.2, 517 (2006).

9. Griffin, J. W. Augustus Waller and the case of

the disappearing axon. Nat. Clin. Pract. Neurol.

3, 355 (2007).

10. Griffin, J. W. The gathering storm. Nat. Clin.

Pract. Neurol. 5, 61 (2009).

Throughout his career, Jack

was always a strong advocate

for the junior members of the

profession

PERIPHERAL NEUROPATHIES

Clinical prognostic scalesin GuillainBarr syndromeNortina Shahrizaila and Nobuhiro Yuki

The clinical presentation o GuillainBarr syndrome (GBS) is

heterogeneous and, despite eective treatments, some patients die

or sustain severe disabilities. An improved clinical prognostic score or

GBS acilitates early identifcation o patients expected to have pooroutcomes. These individuals might beneft rom modifed treatment or

participation in therapeutic trials.

Shahrizaila, N. & Yuki, N. Nat. Rev. Neurol.7, 362363 (2011); published online 21 June 2011;

doi:10.1038/nrneurol.2011.93

the new score can

identify patients with GBSwho have a poor prognosis at

[hospital] admission

GuillainBarr syndrome (GBS) is anacute inflammatory demyelinating polyneuropathy usually triggered by an infection.Since the nearelimination of poliomyelitis,GBS is the most common cause of acuteflaccid paralysis worldwide. However, theclinical presentation of GBS is hetero

geneous, and existing recommendations fortreatment might need to be individualizedto provide the optimal therapeutic option.For this reason, clinical prognostic scorescurrently available for GBS have an important role in determining which treatmentoptions are appropriate for subgroups ofpatients with different prognoses. As earlyprediction of outcome is important for bothselection of treatment options and assessingthe possible benefits of these treatments, agroup based at the University MedicalCenter in Rotterdam, The Netherlands, has

improved on the clinical prognostic scorethey previously developed to predict theoutcome of patients with GBS at an earlierpoint in the disease course.

The Erasmus GBS Outcome Score(EGOS) was the f irst validated prognosticindicator for GBS, which provided a simpleclinical scoring system that could be appliedto patients with this syndrome 2 weeks afterhospital admission.1 EGOS relies on severalvariables (age, the presence of diarrhea andthe disability functional score) that can

2011 Macmillan Publishers Limited. All rights reserved

mailto:ahoke@jhmi.eduhttp://www.nature.com/doifinder/10.1038/nrneurol.2011.93http://www.nature.com/doifinder/10.1038/nrneurol.2011.93mailto:ahoke@jhmi.edu

8/3/2019 nrneurol.2011.93

2/2NATURE REVIEWS|NEUROLOGY VOLUME 7 | JULY 2011 | 363

NEWS & VIEWS

mEGOS could improve

the clinical management of

patients with GBS who have a

poor prognosis

accurately predict the patients chances ofwalking independently at 6 months afterhospital admission. The new version developed by Walgaard et al. has improved onEGOS; the new score can now identifypatients with GBS who have a poor prognosis at admission and 1 week after admission.2 The modified EGOS (mEGOS), as theresearchers call the new score, uses similarpredictive variables, such as age, the occurrence of antecedent diarrhea and the severity of GBS to assess patients at the timeof admission, as well as 7 days after hospitaladmission. However, in mEGOS, the severity of GBS is evaluated using the MedicalResearch Council sum scorethat is, thesum of scores (ranging from 0 [tetraplegic]to 60 [normal]) of six different musclegroups, measured bilaterallyrather thanthe functional grading scale used in theoriginal EGOS. The outcomes measured

were also expanded to include functionalability at 4 weeks, 3 months and 6 monthsafter hospital admission, which is importantto ensure that the new score is useful forthe selection and monitoring of patients inclinical trials of new treatment regimes forpatients predicted to have a poor prognosis.Consequently, mEGOS could potentiallyimprove the clinical approach to and futuremanagement of patients with GBS who havea poor prognosis.

Current evidence from clinical trialsindicates that patients who present with

GBS within 2 weeks of onset of the precipitating illness and are unable to walkwithout help should receive either plasmaexchange or intravenous immunoglobulin(IVIg), both of which will hasten thepatients recovery and improve their outcomes. Although both treatments are effective, GBS is still associated with substantialrates of death and severe disability (between9% and 17%).3 The results of some studieshave also suggested that patients withGBS who have IgG antiganglioside GM1antibodies respond better to IVIg than to

plasma exchange.4,5 Patients with a poorprognosis also often have high titers of IgGantibodies against the motor gangliosidesGM1, GM1b, GD1a or GalNAcGD1a.6Among patients with GBS who receivedIVIg as part of their treatment, those witha small rise in serum IgG levels had worseoutcomes than patients who had a substantial increase in their IgG levels.7 In addition, serological evidence ofCampylobacterjejuni or cytomegalovirus infections arealso associated with lessfavorable outcomes.8,9 Patients with GBS who have a

poor prognosis (that is, who have IgGantiganglioside antibodies, a small rise inserum IgG levels or serological evidenceof C. jejuni or cytomegalo virus) might,therefore, benefit from a second course oran increased dose of IVIg.

Nerve conduction studies form part ofthe diagnostic process, and serial studiesare important to define the subtype of GBS,acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonalneuropathy (AMAN) being the two mainsubtypes. Evidence of inexcitable nerves

and axonal degeneration on neurophysiology are associated with a poor prognosis.9In a typical clinical setting, however, theselaboratory tests may not be easily accessible;in such cases, mEGOS will certainly proveuseful in deciding on the prognosis andtreatment options for each patient.

One of the potential drawbacks ofmEGOS that Walgaard et al. acknowledgeis its unknown utility in populations otherthan white Europeans. Studies suggest thatGBS subtypes differ between Western andAsian populations. AIDP is more frequent

in Western populations, whereas AMANpredominates in Asia.10 As mEGOS wasderived from a white Dutch population, onecould argue that its utility may be restrictedto the AIDP subtype of GBS. However, ifserial nerve conduction studies are not performed, reversible forms of AMAN (such asacute motor conduction block neuropathy)could be missed; therefore, the true incidence of AMAN in Western populationscould be underestimated.10 Future studiesof the mEGOS and EGOS in other populations will be important to clarify the valid

ity of the model in different cohorts withGBS, and a retrospective look at the useof mEGOS and EGOS in the existing GBSdatabases will be important to clarify thevalidity of the model in these cohorts.

Translating the use of these prognosticscales into practice has important implications. Both EGOS and mEGOS use clinical variables that are simple to measure.Furthermore, from a practical perspective,clinicians can use these scales at the timeof hospital admission, as well as at 1 weekand 2 weeks after admission, to quantify

the patients probability of recovering theability to walk without assistance at certaintime frames. However, it should be notedthat other factors, such as the neurophysiological findings and the patientsclinical progress while on treatment, shouldalso be taken into account. The mEGOSshould greatly facilitate the identificationof patients with a poor prognosis, for whoman escalation of treatment should be considered and recruitment into clinical trialsassessing improved treatment modalitiesis vital. International collaborative effortsinitiated by the International InflammatoryNeuropathy Consortium to address theseissues are currently underway; these includethe International GBS Outcomes Study andthe International Second Dose of IVIg inGBS in patients with a poor prognosis.

Division of Neurology, Department of Medicine,

Faculty of Medicine, University of Malaya,Lembah Pantai, 50603 Kuala Lumpur,

Malaysia (N. Shahrizaila). Departments of

Microbiology and Medicine, National University

of Singapore, 5 Science Drive 2, Block MD4A,

Level 5, Singapore 117597 (N. Yuki).

Correspondence to: N. Yuki

micyuki@nus.edu.sg

Competing interests

The authors declare no competing interests.

1. van Koningsveld, R. et al. A clinical

prognostic scoring system for GuillainBarr

syndrome. Lancet Neurol.6, 589594

(2007).

2. Walgaard, C. et al. Early recognition of poor

prognosis in GuillainBarr syndrome.

Neurology76, 968975 (2011).

3. Hughes, R. A. et al. Immunotherapy for

GuillainBarr syndrome: a systematic review.

Brain130, 22452257 (2007).

4. Kuwabara, S. et al. Two patterns of clinical

recovery in GuillainBarr syndrome with IgG

anti-GM1 antibody. Neurology51, 16561660

(1998).

5. Jacobs, B. C. et al.Campylobacter jejuni

infections and anti-GM1 antibodies in

GuillainBarr syndrome.Ann. Neurol.40,

181187 (1996).

6. Jacobs, B. C. et al. Subclass IgG to motor

gangliosides related to infection and clinical

course in GuillainBarr syndrome.

J. Neuroimmunol.194, 181190 (2008).

7. Kuitwaard, K. et al. Pharmacokinetics of

intravenous immunoglobulin and outcome in

GuillainBarr syndrome.Ann. Neurol.66,

597603 (2009).

8. Visser, L. H. et al. Cytomegalovirus infection

and GuillainBarr syndrome: the clinical,

electrophysiologic, and prognostic features.

Neurology47, 668673 (1996).

9. Hadden, R. D. et al. Preceding infections,

immune factors, and outcome in Guillain

Barr syndrome. Neurology56, 758765

(2001).

10. Kuwabara, S. Axonal GuillainBarr syndrome

is underestimated in Europe?J. Neurol.

Neurosurg. Psychiatry81, 1063 (2010).

2011 Macmillan Publishers Limited. All rights reserved

mailto:micyuki@nus.edu.sgmailto:micyuki@nus.edu.sg