neuropo

Vol. 48 - No. 3 EUROPEAN JOURNAL OF PHYSICAL AND REHABILITATION MEDICINE 507

Rehabilitation interventions in patients with acute demyelinating inflammatory

polyneuropathy: a systematic review

disciplinary rehabilitation up to 12 months. Evidence for uni-disciplinary rehabilitation interventions is lim-ited, with ‘satisfactory’ evidence for physical therapy in reducing fatigue, improving function and quality of life in persons with GBS. This review provides “good” evidence to support multidisciplinary rehabilitative intervention in adults with GBS; and “satisfactory” ev-idence for physical therapy in these patients. Evidence for other uni-disciplinary interventions is limited or inconclusive. The gaps in existing research should not be interpreted as ineffectiveness of rehabilitation in-tervention in GBS. Further research is needed with appropriate study designs, outcome measurement, type of modalities and cost-effectiveness of these in-terventions.Key words: �Guillain-Barre syndrome - Rehabilitation - Disa-bled persons.

Acute inflammatory demyelinating polyneu-ropathy or Guillain-Barré Syndrome (GBS) is a

group of disorders due to inflammation of periph-eral nerves and nerve roots, which lead to rapidly developing motor deficits (symmetrical ascending paralysis), autonomic dysfunction, sensory deficits and respiratory failure.1-3 GBS usually reaches a na-dir within four weeks from onset.4, 5 It is recognized as a heterogeneous syndrome with several variants,

1Department of Medicine, Dentistry and Health SciencesUniversity of Melbourne, Parkville, Australia

2Department of Rehabilitation MedicineRoyal Melbourne Hospital, Parkville, Australia

3School of Public Health and Preventive MedicineMonash University, Victoria, Australia

EUR J PHYS REHABIL MED 2012;48:507-22

F. KHAN 1-3, B. AMATYA 2

Acute inflammatory demyelinating polyneuropathy (Guillain-Barré syndrome, GBS) can be a significant cause of new long-term disability, which is thought to be amenable to rehabilitation. Rehabilitation is an ex-pensive resource and the evidence to support its jus-tification is urgently needed. This systematic review presents an evidence-based overview of the effective-ness of various rehabilitation interventions in adults with GBS and the outcomes that are affected. Medline, EMBASE, CINAHL, AMED, PEDro, LILACS and the Co-chrane Library were searched up to March 2012 for studies reporting outcomes of GBS patients following rehabilitation interventions that addressed functional restoration and participation. Two reviewers applied the inclusion criteria to select potential studies and independently extracted data and assessed the meth-odological quality. Included studies were critically appraised using GRADE methodological quality ap-proach. Formal levels of evidence of each intervention were assigned using a standard format defined by National Health and Medical Research Council. Four-teen papers (one systematic review, one randomized controlled trial, one case-control study, five cohort studies and six case series/reports) that described a range of rehabilitation interventions for persons with GBS were evaluated for the “best” evidence to date. One high quality randomised controlled trial demon-strated effectiveness of higher intensity multidiscipli-nary ambulatory rehabilitation in reducing disability in persons with GBS in the later stages of recovery, compared with lesser intensity rehabilitation inter-vention for up to 12 months. Four observational stud-ies, further demonstrated some support for improved disability and quality of life following inpatient multi-

Corresponding author: F. Khan, MBBS, MD, FAFRM (RACP), De-partment of Rehabilitation, Royal Melbourne Hospital, 34-54 Poplar Road Parkville, Melbourne VIC 3052, Australia. E-mail: [email protected]

Anno: 2012Mese: SeptemberVolume: 48No: 3Rivista: EUROPEAN JOURNAL OF PHYSICAL AND REHABILITATION MEDICINECod Rivista: EUR J PHYS REHABIL MED

Lavoro: titolo breve: Rehabilitation interventions in patients with acute demyelinating inflammatory polyneuropa-thyprimo autore: KHANpagine: 1-2

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KHAN REHABILITATION INTERVENTIONS IN PATIENTS wITH ACUTE DEMYELINATING INFLAMMATORY POLYNEUROPATHY

508 EUROPEAN JOURNAL OF PHYSICAL AND REHABILITATION MEDICINE September 2012

most common type being acute inflammatory demy-elinating polyradiculoneuropathy.6 Table I lists the various variants of GBS.7

GBS has a reported male preponderance 8 and can occur at any age (usually older individuals, but common between ages 30 and 50 years). The world-wide annual incidence is estimated to be 1-2 per 100,000, and rarely it has geographical clustering.9,

10 In developed countries, GBS incidence has been stable and mortality has been reduced to 2-3% but this is higher in the developing world.9, 11 Overall mortality associated with GBS is low; approximately 3% of patients may die of complications in the acute phase of GBS.11 The progressive phase usually is limited to four weeks and generally most patients have a favorable outcome; however, the majority of patients are ambulant within six months from onset of symptoms.12 Despite this, disease course may be fulminating in 30% of patients with a rapid progres-sion requiring ventilatory support within a couple of days (involvement of respiratory and bulbar mus-cles),1 and 20% may have residual permanent se-vere disability, with deficits in ambulation or require ventilator assistance 12 months later.13 Autonomic dysfunction (sinus tachycardia or bradycardia, fluc-tuating hypertension or hypotension, flushing of the face, loss of or excessive sweating) occurs in 70% and is associated with sudden death.3 Facial weakness occurs in more than half of the patients.1 A number of factors, including preceding diarrhea, older age, rapid progression, disability at nadir and specific neurophysiological parameters have been associated with poor outcome.14, 15

Information on longer-term sequelae of GBS and their impact on everyday life are sparse. One study (N.=76) reported that despite good functional recov-ery up to 14 years post GBS (median six years, range 1-14), 16% of patients continued to report moderate to extreme impact on work, family and social activi-

ties; and 22% reported ongoing substantial impact on mood, confidence and ability to live independ-ently.16 Other studies show that psychosocial per-formance does not necessarily correlate with the se-verity of impairment in GBS, but may be explained by poor conditioning and fatigue.17, 18 Approximately 40% of all case require intensive inpatient rehabilita-tion 4 and can present to rehabilitation settings with a wide array of physical, emotional, psychosocial and/or environmental difficulties. These disabilities can have a cumulative effect over time and cause considerable distress to the GBS survivor (and their families), and reduce their quality of life (QoL).16, 19 These can limit their function and participation with high impact on daily activities, vocational and social activities (work, family and intimate relationships, community/social congregation).

The world Health Organization, International Classification of Functioning, Disability and Health (ICF),20 provides an standard framework for disabil-ity and participation in various health conditions, including contextual factors. Rehabilitative care uses the terminology of this classification system to de-scribe the impact of disease at different levels. For example, in a GBS survivor:

— “impairments” are problems with body (ana-tomical) structures or (physiological) function (pa-ralysis, inability to swallow, pain);

— “activity limitations” (disability) are difficulties faced by a person executing everyday tasks (mobil-ity or self-care);

— “restrictions in participation” relate to prob-lems that limit involvement in social and other life situations (employment, family life);

— “contextual factors”, which may affect the per-son’s experience of living with their condition:

− “environmental”: the physical, social and attitudinal environment in which people live their lives; and

− “personal”: such as gender, race, coping style, social and educational background.

with advances in medical treatment and decreased mortality rates, the emphasis is on provision of in-tegrated care to GBS survivors over a longer period, as these individuals are often young.16 Rehabilitation intervention can be important in the longer-term as the management of physical and psychosocial se-quelae impact activity and participation. Its principal focus is on reducing symptoms and limitations at the level of a person’s activity and participation (in-

Table � I.—�Acute inflammatory polyneuropathy variants (≤4 weeks progressive phase).

Guillain–Barré syndrome (GBS) – acute inflammatory demyelinating polyradiculoneuropathy (AIDP) – acute motor axonal neuropathy (AMAN) – acute motor and sensory axonal neuropathy (AMSAN)

Miller Fisher syndrome (cranial nerve involvement)Miller Fisher/GBS overlap syndrome – acute sensory demyelinating neuropathy – acute pandysautonomia

From Hughes RAC.7

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REHABILITATION INTERVENTIONS IN PATIENTS wITH ACUTE DEMYELINATING INFLAMMATORY POLYNEUROPATHY KHAN


bilitation interventions in GBS survivors, or stud-ies that compared rehabilitation interventions with routinely available local services or lower levels of intervention in different settings or at different lev-els of intensity that included outcome measures (as defined by the ICF 20) addressing impairments, dis-ability and/or participatory issues, were included, ir-respective of the study design. Systematic reviews (SR), meta-analyses (MA), and randomised control-led trials (RCT) were given high priority. where high level evidence was not available or where there was a paucity of publications, lower levels of evidence were reviewed e.g. clinical controlled trials, control-led before-and-after studies, before-and-after studies without a concurrent control, cohort, case-control studies, and case series. Descriptive studies for ef-fectiveness of rehabilitation were also scrutinised to identify gaps in service provision.

Both authors (FK, BA) independently screened and short-listed all abstracts and titles of studies identified by the search strategy for inclusion and appropriateness based on the selection criteria. Each study was independently evaluated by authors. If necessary, full text of the article was obtained for further assessment to determine if the trial met the inclusion/exclusion criteria. If no consensus was met about the possible inclusion/exclusion of any indi-vidual study, a final consensus decision was made between the authors. Further information about the complete description of rehabilitation interventions from the trialists was obtained, where necessary. Both authors (FK, BA) independently extracted the data using a standard proforma, which included: publication date and country, study location, study design, sample size, intervention and outcomes. Any discrepancies were resolved by re-reviewing the study by both authors.

Authors (FK, BA) critically appraised all included trials based on GRADE methodological quality from the domains: sequence generation, allocation con-cealment, blinding of participants, therapists and outcome assessors, incomplete outcome data and selective outcome reporting.22 A “yes” indicates a low risk of bias, while “no” a high risk of bias, and “unclear” an unclear or unknown risk of bias. Stud-ies were considered to be of “high methodological quality” if the risk of bias for all domains was low. Studies were rated as “low methodological quality” if there was unclear or high risk of bias for one or more domains.22

cluding personal and environmental factors). Reha-bilitation in person with GBS extends beyond acute management, to restoration of patient’s previous daily activities and reintegration into the home and community.

To our knowledge, there is no systematic evalu-ation of published studies of various rehabilitation interventions in persons with GBS. Therefore, this review presents an overview of existing evidence for the effectiveness of rehabilitation interventions in adults with GBS.

Methods

A comprehensive search of peer reviewed lit-erature was conducted using electronic databases; MEDLINE (1980-March 2012), Cochrane library (latest issue 2012), EMBASE (1980- March 2012), CINAHL (1982- March 2012), AMED (1985-March 2010), and LILACS (1982- March 2012). A search for systematic reviews (filter) using the PubMed data-base was conducted, and PubMed Clinical alerts was set up to identify literature published till March 2012. Medical subject heading (MeSH) search terms were used for all databases and a keyword search was used if the MeSH term was not available, which included: “acute inflammatory demyelinating polyr-neuropathy” or “Guillain-Barre Syndrome” or “GBS” or ”acute inflammatory demyelinating polyradicu-loneuropathy”, or “AIDP” or “acute motor axonal neuropathy and acute motor and sensory axonal neuropathy” or “Miller Fisher syndrome” or “acute pan-dysautonomia” combined using AND with “ambulatory care” or “rehabilitation” or “hospitali-zation” or “home care services, hospital-based” or “inpatients” or “outpatients” or “multidisciplinary” or “interdisciplinary or integrated or multimodal”, or “physical therapy modalities” or “physical therapy or exercise” or “cognitive or psychological therapy”, “behavior therapy”, “occupational therapy” or “social work” or “dietetics” or “dietary services” or “counsel-ling”. Publication bias was minimized by sourcing unpublished data where possible.21 Bibliographies of papers identified were scrutinised, and authors and known experts in the field were contacted seek-ing published and unpublished trials. Limits placed included English language publication; and adults aged 18 and over.

Studies that evaluated the effectiveness of reha-

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— strong evidence: several level I or II studies of high quality;

— good evidence: one or two level I or level II studies of high quality or a systematic review/multi-ple level III studies of high quality;

— satisfactory evidence: level III studies of high quality or level I or II studies of moderate quality;

— poor evidence: level IV studies or low quality level I to III studies.

This review did not intend to summarise evidence for effectiveness of specific pharmacological agents and other non-pharmacological alternative/conserv-ative interventions.

Results

Article retrieval

The search retrieved 494 articles, of which six ar-ticles were duplicates. Of the 488 articles screened, 35 met the abstract inclusion criteria. Four articles that met the abstract inclusion criteria were identi-fied from the bibliographies of relevant articles or from the PubMed email alerts. Eight articles (one systematic review, one RCT, one case-control study and five cohort studies) met the methods review inclusion criteria. All primary studies were criti-cally appraised using GRADE approach (Table III). Other case series/case reports (N.=6) were con-sidered to be supportive evidence and were sum-marised while describing the relevant sections. No cost-analysis studies were identified by the search strategy.

where high quality SR or MA were identified, ar-ticles published prior to the date of that review’s search strategy were excluded.

Evidence was categorised according to study de-sign using a hierarchy of evidence in descending order. Formal levels of evidence were assigned us-ing a standard format defined by National Health and Medical Research Council (NHMRC) pilot pro-gramme 2005-2006 for intervention studies (Table II).23

The evidence base was summarised using the fol-lowing terminology and definitions:23

Table � II.—�Designations of levels of evidence according to type of study.

Level Intervention

I A systematic review of level II studiesII A randomised controlled trialIII-1 A pseudo-randomised controlled trial

(i.e., alternate allocation or some other method)*III-2 A comparative study with concurrent controls

– Non-randomised experimental trial (including controlled before-and-after study)

– Cohort study – Case-control study – Interrupted time-series with a control group

III-3 A comparative study without concurrent controls – Historical control study – Two or more single arm study – Interrupted time-series without a parallel control group

IV Case series with either post test or pre test/post test (also known as before-and-after study) outcomes

Adapted from NHMRC 2009.23 *This also includes controlled before-and-after studies, as well as indirect comparisons.

Table �III.—�Levels of quality of individual studies (GRADE approach 22).

Bias Khan et al. 2011 24

Gupta et al. 2010 32

Demir and Koseoglu 2008 28

Nicholas et al. 2000 30

El Mandi et al.2007 33

Garssen et al. 2004 34

Meythaler et al. 1997 29

Random sequence generation (selection bias)

- + + + + + +

Allocation concealment (selection bias)

- + + + + + +

Blinding of participants and personnel (performance bias)

- + + + + + +

Blinding of outcome assessments (detection bias)

- + + + + + +

Selective reporting (reporting bias)

- ? - - + ? +

Other bias - + + + + + +Study quality rating High Very low Very low Very low Very low Very low Very low

+ = high risk; - = low risk; ? = unclear risk.

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ventilatory support who are generally more severely disabled with an extended period of disease na-dir.13 A rehabilitation approach to GBS includes a wide spectrum of treatments. The existing evidence for specific rehabilitation interventions in GBS are summarised below, categorised according to study design using hierarchy of evidence in descending order. The most recently published high quality

A flow chart outlining the different phases of arti-cle retrieval processes is displayed in Figure 1.

Evidence for GBS rehabilitation

More than a third of all GBS patients require in-patient rehabilitation, particularly those requiring

Articles identified by electronic searching (N.=494)

Articles screened after duplicates removed (N.=488)

Articles excluded after title and abstract review(N.=453)

Full-text articles assessed for eligibility (N.=35)

Studies included in systematic review (N.=14)

Systematic review=1RCT=1

Case-control study=1Cohort study=5

Case-series/report=6

Additional studies identified by cross-referencing (N.=4)

Full-text articles excluded, (N.=25)

[Not interventional studies =20Not English language=3

No data on GBS= 2]

Incl

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Iden

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Elig

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Figure 1.—Flow diagram showing selection of article review.MIN

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The search strategy further identified one recently conducted RCT.31 This high quality RCT 31 (N.=79) evaluated the effectiveness of MD ambulatory reha-bilitation in person with GBS after the initial posta-cute phase (median 6.5 years since diagnosis), com-paring high intensity MD rehabilitation programme with low-intensity rehabilitation programme over 12 months. The intensive rehabilitation programme in-cluded individualized, functional goal-oriented MD treatment with active patient participation. The treat-ment programme included up to three one-hour ses-sions of therapy/week, comprising half-hour blocks of therapy sessions (Occupational, Social, Psycholo-gy, Speech and Physiotherapist,), two to three times per week for up to 12 weeks. The methods used for example included physiotherapy for strength-ening, endurance and gait training; occupational therapy to improve everyday function (domestic, community tasks), driving and return to work; and clinical psychology for counselling and support as required. The study demonstrated a benefit of MD rehabilitation programme for reduced motor dis-ability (mobility, self-care, continence programme) and participation (relationships). High-intensity re-habilitation programmes were effective using both “per protocol” and “treatment-based” analyses. Over the study period, more participants in the treatment group improved compared with controls (68.6% vs. 32.4%), and more participants in the control group reported deterioration in function compared with the treatment group (41.2% vs. 2.9%); this difference was statistically significant (P<0.001).31

Another prospective cohort study (N.=35) evaluat-ing the comprehensive inpatient MD neurorehabili-tation, reported significant functional recovery for longer period (up to 1 year).32 The authors found that patients had GBS-related residual motor and sensory deficits at one year, these included: neu-ropathic pain, foot drop necessitating ankle-foot orthosis, and locomotion difficulties requiring as-sistive devices. Inpatient rehabilitation programme, and post discharge individualised home-based pro-gramme (formulated by physiotherapists and occu-pational therapists), consisted of range of motion exercises (passive, active assistive, active or active resistive) for the limbs, deep breathing exercises in patients with respiratory difficulties, home modifica-tions for access, gait training with or without splints, assistive devices and activities of daily living (ADL) skills training. The authors found significant over-

systematic reviews or meta-analysis and RCTs were prioritized. A quantitative analysis of studies was not possible due to the use of diverse interventions and outcome measures; and clinical heterogeneity. Therefore, a best-evidence synthesis is presented to summarize the results of the included studies. Sum-mary of the included studies are shown in Table IV.

Multidisciplinary rehabilitation

In this review multidisciplinary (MD) rehabilita-tion is defined as the “co-ordinated delivery of inter-vention by two or more disciplines (physiotherapy, occupational therapy, social work, psychologist and other allied health, nursing), under medical super-vision (neurologist, rehabilitation physician)”.24 MD rehabilitation is designed to be patient-centred, time-based, functionally-oriented and aims to maximise activity and participation (social integration) using a biopsychosocial model.24 Existing clinical guidelines and frameworks 25, 26 for GBS, recommend compre-hensive, flexible coordinated MD care and appropri-ate follow-up, education and support for patients (and carers).

A recent systematic review of MD rehabilitation in person with GBS 27 did not identify any RCTs or CCTs. However, evidence from three observational studies supported the effectiveness of MD rehabili-tation programmes in inpatient settings in terms of improvements in activity (disability) and participa-tion for up to six months.27 These three studies 28-30 were conducted in inpatient rehabilitation settings in three different countries (Turkey, United Kingdom and United States) with a total of 128 participants (Table IV). All studies were rated as “very low qual-ity”. All demonstrated an improvement in disability from the time of inpatient rehabilitation admission to discharge in a timeframe shorter than 12 months. In addition, one study 28 showed an improvement in disability at six-month follow-up after rehabilita-tion. Evidence in regards to improvement in QoL during or after rehabilitation was inconclusive. All three studies included patients with severe GBS with high levels of physical dependency, which limits the generalisation of the results to patients with less se-vere GBS. The authors highlighted a need of future research using robust study design, using appropri-ate outcome measures, optimal intensity, frequency and cost-effectiveness of rehabilitation therapy over a longer time period.27

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tion of motor units with regular muscle use to gen-erate large but sub-maximal forces and suggested for more intense and longer-term rehabilitation pro-grammes (for minimum of 24 months) to enhance recovery in these patients.33

Another prospective cohort study evaluated ef-fectiveness of a 12-week bicycle exercise training in 20 patients with polyneuropathy (including 16 with GBS) with severe fatigue.34 The findings dem-onstrated that bicycle training was well tolerated by participants and showed significant beneficial effect on physical fitness, functional outcome, and QoL of these patients. There was a significant improvement in the post-intervention fatigue score (decreased by 20%, P=0.001). Further, majority of the participants (80%) were motivated to continue with regular train-ing activities.34

Bussmann et al.35 in a case series explored the effects of physical exercise in severely fatigued patients with GBS and chronic inflammatory de-myelinating polyneuropathy to clarify the mutual relationships between various domains: physical fit-ness, fatigue, objectively measured actual mobility, perceived physical functioning, and perceived men-tal functioning. The authors reported that physical exercise resulted in improved fitness, however this did not influence changes in fatigue, actual mobility and perceived functioning. Significant relationships were found between the domains: perceived mental functioning and actual mobility, perceived mental functioning and perceived physical functioning, and between fatigue and perceived physical functioning.

A case report conducted earlier, reported effec-tiveness of neuro-developmental sequencing, incor-porating development of motor control and gross motor skills using neuro-developmental positions (i.e., from supine to sitting to standing) with range of motion and strengthening exercises at each stage, particularly in a geriatric patient.36 Another, case study demonstrated effectiveness of supervised en-durance training programme in improving cardiop-ulmonary and work capacity, and isokinetic strength of legs.37

The use of digital gait analysis,38 partial body weight support systems,39 precutaneous kyphoplasty 40 and podiatrons (a mechanized rotating platforms) 41 have also been explored with limited success.

Reports suggest that care should be taken not to overwork muscle groups 42 and exercise programs should initially be non-fatiguing, and as muscles

all functional recovery by participants in all meas-ures: Modified Barthel Index scores (MBI), Modified Rankin Scale (MRS) and Hughes Disability Scale (HDS) (P<0.001 each) at the time of discharge and at one year follow-up (P<0.01 for all, except for MBI P=0.002).32

Specific rehabilitation interventions

A number of rehabilitative treatments have been proposed for persons with GBS. This review, how-ever found limited number of studies evaluating these interventions. Moreover, many interventions have not yet carried into comprehensive MD reha-bilitation programs, and few studies show its imple-mentation. The existing evidence for various specific rehabilitation interventions in GBS are summarised below.

PhysIcal �TheraPeuTIc �modalITIes

Improving or restoring physical abilities is a key issue in rehabilitation of GBS patients. Physi-cal therapeutic modalities involve a graduated mo-bility programme, which includes maintenance of posture and alignment, maintaining joint range of motion, provision of orthotics, endurance and mus-cle strengthening, and progressive ambulation pro-gramme using adaptive gait aids.26 The literature investigating effectiveness of physical therapeutic modalities is sparse.

Physical therapy/Exercise.—El Mhandi et al.33 in a prospective cohort study (N.=6) showed significant muscle strength improvement using dynamomet-ric measures at 18 months following an individual-ized physical therapy programme based on muscu-lar reinforcement and active mobilization (average 2-3 weekly sessions). The authors found that at six months, manual muscle testing and functional inde-pendence motor total scores were close to normal levels; and at 18 months, all patients satisfied the criteria for a full recovery. Compared to matched healthy controls, isometric and isokinetic strength increased significantly during the first six months (P<0.01), though muscle strength increased less rap-idly (P<0.05) between 6 and 18 months. There was a significant negative correlation between plateau period duration and knee extensors, elbow flexors muscles strength recovery (P=0.05). The authors credited this improvement to increased synchroniza-

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Table �IV.—�Summary of included studies.

Study (author, year, country); Design, participants (N.) Study objective Intervention Main findings Level of evidence*

Multidisciplinary careKhan et al.,19

2010Australia

Systematic review(total included studies = 3 observational studies)

To assess the effectiveness of MD care in adults with GBS, especially the types of approaches that are effective (settings, intensity) and the outcomes that are affected

MD rehabilitation care: any co-ordinated intervention delivered by two or more disciplines (nursing, physiotherapy, occupational therapy, speech pathology, orthotics, dietetics, social work, psychology or neuropsychology), under medical supervision, which aims to limit patient symptoms, enhance functional independence and maximise participation

– No randomised controlled trials or controlled clinical trials were identified. – Best evidence to date comes from three ‘very low quality’ observational studies, which provide some support for improved disability in the short term (less than 6 months); and QoL, as measured by a reduction in handicap (participation) with high intensity inpatient MD rehabilitation

I

Khan et al.,24

2011Australia

RCT(N.=79)

To assess the effectiveness of a high- vs. low-intensity MD ambulatory (outpatient) rehabilitation programme over 12 months for persons in the chronic phase after GBS

Treatment group - individualized high intensive ambulatory (outpatient) MD rehabilitation programme, up to 3 one-hour sessions of interrupted therapy/week, comprising half-hour blocks of therapy sessions (Occupational, Social, Psychology, Speech and Physiotherapist), two to three times per week for up to 12 weeksControl group- low intensive home based programme of maintenance exercises and education for self management with a 30 minute physical programme (walking, stretching) twice weekly and usual activity at home

– Reduction in disability in the treatment group in post-treatment FIM domains (mobility, transfers, sphincter control and locomotion; all P<0.005) and PIPP scores (relationships; p=0.011), with moderate-to-small effect sizes (r=0.36-0.23).

– Over the study period, more participants in the treatment group improved compared with controls (68.6% vs. 32.4%), and more participants in the control group reported deterioration in function compared with the treatment group (41.2% vs. 2.9%); this difference was statistically significant (P<0.001).

– In sub analysis (comparison of groups based on treatment status irrespective of randomisation status), significant differences, associated with large effect sizes (r<0.5) in the change scores between the treated (high intensity rehabilitation) (N.=31) and low-intensity rehabilitation treatment (N.=38) groups were detected for the FIM total and each motor subscales (P<0.001 for all). There was no significant change in scores for DASS and wHOQoL subscales, except for the PIPP “relationship” subscale (P=0.028).

II

Gupta et al.,32

2010India

Prospective longitudinal cohort study (without control)(N.=35)

To analyse long-term functional recovery, deficits and requirement of lower limb orthosis for locomotion in patients with GBS

Inpatient rehabilitation programme, and post discharge individualised home-based programme (formulated by physiotherapists and occupational therapists): ROM exercises (passive, active assistive, active or active resistive) for the limbs, deep breathing exercises, modifications at home with full accessibilities for the patients, gait training with or without splints and assistive device and ADLs skills training

Primary outcome: – Twenty-one patients (60%) had foot drop and advised ankle-foot orthosis, 30 patients (85.71%) needed assistive devices also for locomotion at discharge. After 1 year, foot drop was still present in 12 patients (34.28%) using orthosis.

– LOS= mean 32.9±16.4 days. Significant correlation (P=0.004) was found between LOS in and patients having autonomic dysfunction. No significant correlation (P>0.05) was observed between LOS and requirement of assisted ventilation, cranial nerve involvement during acute phase, requirement of lower limb orthosis and admission scores

Secondary outcome: – Patients showed significant recovery using all MBI, MRS, and HDS scales (P<0.001 each) at the time of discharge and at one year follow-up in all scores (P<0.01 for all, except for MBI P=0.002)

III-3

Demir and Koseoglu,28

2008Turkey

Case-control study(N.=65: intervention =34, control =31)

To compare the HRQoL in control subjects and patients with severe GBS 6 months after rehabilitation and to determine the relationship of several sociodemographic and medical factors with the HRQOL of the GBS survivors

Inpatient rehabilitation programme - no further description providedControl: healthy controls - no intervention

– Improvements in disability as measured by FIM gains from admission to discharge (P=0.001) and also at 6 months after rehabilitation (P=0.001).

– GBS patients had poorer HRQoL at six-months after rehabilitation compared with healthy controls in all domains of the Nottingham Health Profile (NHP): physical mobility, energy, pain, sleep, social isolation and emotional reactions, P<0.001 for all domains).

– Being a female, employment, mechanical ventilation, a tendency to depression and educational status were found to be associated with poor HRQoL.

III-2

Meythaler et al.,29

1997USA

Retrospective cohort study without controls(N.=39)

To determine associations between early variables (requirement for ventilator support, anemia, proprioception, vibratory, fine touch/pinprick, deep-tendon reflexes, cranial nerve involvement dysautonomia, electrodiagnostic findings, plasmapheresis, age, and gender) and outcome variables

Individualised inpatient MD rehabilitation programme with 3 to 4 hours daily of physical and occupational therapy, and psychology and speech therapy if indicated.

– Activity limitation <12 months – Reduction in disability as FIM scores improved from admission to discharge – FIM motor score improved by an average of 15.7 points from mean admission score of 34.7 to mean discharge score of 50.3.

– FIM cognitive score improved by an average of 6.9 points from mean admission score of 78.1 to mean discharge score of 85.

III-3

Nicholas et al.,30

2000UK


To determine the outcome in severe GBS following combined neurological and rehabilitation management and to identify the factors which affect this outcome

Individualised inpatient MD rehabilitation (consultant neurologist, clinical nurse specialist, two sessions of physiotherapy and one session of occupational therapy daily, and if required, speech pathology and psychology)

– Activity limitation <12 months: improvement in FIM and BI scores at discharge compared to admission scores: Mean modified BI score increased from 10 to 19; Mean FIM score increased from 53 to 85.

– QoL <12 months - Environmental Status Scale (ESS) (N.=15) decreased from 23 to 13, Handicap Assessment Scale (HAS) (N.=9) decreased from 19 to 10 indicating a reduction in handicap.

III-3

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Multidisciplinary careKhan et al.,19

2010Australia

Systematic review(total included studies = 3 observational studies)

To assess the effectiveness of MD care in adults with GBS, especially the types of approaches that are effective (settings, intensity) and the outcomes that are affected

MD rehabilitation care: any co-ordinated intervention delivered by two or more disciplines (nursing, physiotherapy, occupational therapy, speech pathology, orthotics, dietetics, social work, psychology or neuropsychology), under medical supervision, which aims to limit patient symptoms, enhance functional independence and maximise participation

– No randomised controlled trials or controlled clinical trials were identified. – Best evidence to date comes from three ‘very low quality’ observational studies, which provide some support for improved disability in the short term (less than 6 months); and QoL, as measured by a reduction in handicap (participation) with high intensity inpatient MD rehabilitation

I

Khan et al.,24

2011Australia

RCT(N.=79)

To assess the effectiveness of a high- vs. low-intensity MD ambulatory (outpatient) rehabilitation programme over 12 months for persons in the chronic phase after GBS

Treatment group - individualized high intensive ambulatory (outpatient) MD rehabilitation programme, up to 3 one-hour sessions of interrupted therapy/week, comprising half-hour blocks of therapy sessions (Occupational, Social, Psychology, Speech and Physiotherapist), two to three times per week for up to 12 weeksControl group- low intensive home based programme of maintenance exercises and education for self management with a 30 minute physical programme (walking, stretching) twice weekly and usual activity at home

– Reduction in disability in the treatment group in post-treatment FIM domains (mobility, transfers, sphincter control and locomotion; all P<0.005) and PIPP scores (relationships; p=0.011), with moderate-to-small effect sizes (r=0.36-0.23).

– Over the study period, more participants in the treatment group improved compared with controls (68.6% vs. 32.4%), and more participants in the control group reported deterioration in function compared with the treatment group (41.2% vs. 2.9%); this difference was statistically significant (P<0.001).

– In sub analysis (comparison of groups based on treatment status irrespective of randomisation status), significant differences, associated with large effect sizes (r<0.5) in the change scores between the treated (high intensity rehabilitation) (N.=31) and low-intensity rehabilitation treatment (N.=38) groups were detected for the FIM total and each motor subscales (P<0.001 for all). There was no significant change in scores for DASS and wHOQoL subscales, except for the PIPP “relationship” subscale (P=0.028).

II

Gupta et al.,32

2010India

Prospective longitudinal cohort study (without control)(N.=35)

To analyse long-term functional recovery, deficits and requirement of lower limb orthosis for locomotion in patients with GBS

Inpatient rehabilitation programme, and post discharge individualised home-based programme (formulated by physiotherapists and occupational therapists): ROM exercises (passive, active assistive, active or active resistive) for the limbs, deep breathing exercises, modifications at home with full accessibilities for the patients, gait training with or without splints and assistive device and ADLs skills training

Primary outcome: – Twenty-one patients (60%) had foot drop and advised ankle-foot orthosis, 30 patients (85.71%) needed assistive devices also for locomotion at discharge. After 1 year, foot drop was still present in 12 patients (34.28%) using orthosis.

– LOS= mean 32.9±16.4 days. Significant correlation (P=0.004) was found between LOS in and patients having autonomic dysfunction. No significant correlation (P>0.05) was observed between LOS and requirement of assisted ventilation, cranial nerve involvement during acute phase, requirement of lower limb orthosis and admission scores

Secondary outcome: – Patients showed significant recovery using all MBI, MRS, and HDS scales (P<0.001 each) at the time of discharge and at one year follow-up in all scores (P<0.01 for all, except for MBI P=0.002)

III-3

Demir and Koseoglu,28

2008Turkey

Case-control study(N.=65: intervention =34, control =31)

To compare the HRQoL in control subjects and patients with severe GBS 6 months after rehabilitation and to determine the relationship of several sociodemographic and medical factors with the HRQOL of the GBS survivors

Inpatient rehabilitation programme - no further description providedControl: healthy controls - no intervention

– Improvements in disability as measured by FIM gains from admission to discharge (P=0.001) and also at 6 months after rehabilitation (P=0.001).

– GBS patients had poorer HRQoL at six-months after rehabilitation compared with healthy controls in all domains of the Nottingham Health Profile (NHP): physical mobility, energy, pain, sleep, social isolation and emotional reactions, P<0.001 for all domains).

– Being a female, employment, mechanical ventilation, a tendency to depression and educational status were found to be associated with poor HRQoL.

III-2

Meythaler et al.,29

1997USA


To determine associations between early variables (requirement for ventilator support, anemia, proprioception, vibratory, fine touch/pinprick, deep-tendon reflexes, cranial nerve involvement dysautonomia, electrodiagnostic findings, plasmapheresis, age, and gender) and outcome variables

Individualised inpatient MD rehabilitation programme with 3 to 4 hours daily of physical and occupational therapy, and psychology and speech therapy if indicated.

– Activity limitation <12 months – Reduction in disability as FIM scores improved from admission to discharge – FIM motor score improved by an average of 15.7 points from mean admission score of 34.7 to mean discharge score of 50.3.

– FIM cognitive score improved by an average of 6.9 points from mean admission score of 78.1 to mean discharge score of 85.

III-3

Nicholas et al.,30

2000UK


To determine the outcome in severe GBS following combined neurological and rehabilitation management and to identify the factors which affect this outcome

Individualised inpatient MD rehabilitation (consultant neurologist, clinical nurse specialist, two sessions of physiotherapy and one session of occupational therapy daily, and if required, speech pathology and psychology)

– Activity limitation <12 months: improvement in FIM and BI scores at discharge compared to admission scores: Mean modified BI score increased from 10 to 19; Mean FIM score increased from 53 to 85.

– QoL <12 months - Environmental Status Scale (ESS) (N.=15) decreased from 23 to 13, Handicap Assessment Scale (HAS) (N.=9) decreased from 19 to 10 indicating a reduction in handicap.

III-3

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Phyciacal therapy/exercise

El Mhandi et al.,33

2007France

Prospective cohort study without controls (N.=6)

To assess the recovery in muscle strength and functional capacities in subjects with GBS for 18 months after onset

Individualized physical therapy programme based on muscular reinforcement and active mobilization (average 2-3 weekly sessions)

– At six months, manual muscle testing and functional independence motor total scores were close to normal levels; and at 18 months, all patients satisfied the criteria for a full recovery.

– Compared to the matched healthy controls, isometric and isokinetic strength increased significantly during the first six months (P<0.01), though muscle strength increased less rapidly (P<0.05) between 6 and 18 months.

– There was a significant negative correlation between plateau period duration and knee extensors, elbow flexors muscles strength recovery (P=0.05).

III-3

Garssen et al.,34

2004Netherlands

Prospective cohort study without controls(N.=20)

To investigate feasibility and effect of bicycle training programme on fatigue severity, physical fitness, muscle strength, functional outcome, anxiety and depression, handicap, and QoL

Structured 12-week bicycle exercise training programme

– Bicycle training was well tolerated by the participants. – Significant beneficial effect was noted on physical fitness, functional outcome, and QoL. – There was a significant improvement in the post-intervention fatigue score (decreased by 20%, P=0.001). – Majority of the participants (80%) were motivated to continue with regular training activities.

III-3

Bussmann et al.,35

2007Netherlamds

Case series (N.=20, including 6 with CIDP)

To explore the effects of physical exercise in severely fatigued patients with GBS and CIDP and to clarify the mutual relationships between various domains: physical fitness, fatigue, objectively measured actual mobility, perceived physical functioning, and perceived mental functioning

3 supervised cycle training sessions per week, for 12 weeks period

– Physical exercise resulted in improved fitness, however this did not influence in changes in fatigue, actual mobility and perceived functioning.

– Significant relationships were found between the domains: perceived mental functioning and actual mobility, perceived mental functioning and perceived physical functioning, and between fatigue and perceived physical functioning.

IV

Tuckey and Greenwood,39

2004UK

Case report(N.=1)

To evaluate the effectiveness of partial body weight support (PBwS) during remobilisation after severe GBS

Partial body weight support (Biodex unweighting support system), which makes possible to calibrate the percentage of bodyweight supported and can be used either over a treadmill or on the ground

– PBwS enabled the patient to practise walking. – Between 30-38 weeks post-onset of GBS patient was able to walk with gradually reducing PBwS at a time when he was unable even to stand without PBwS except in an electric standing frame.

– PBwS enabled patient to start task-specific gait retraining eight weeks before it would otherwise have been possible. – At 38 weeks without PBwS he walked 15 metres with a pulpit frame and the assistance of two therapists, and was managing to walk 110 metres on the treadmill with 30 kg PBwS

– At 42 weeks without PBwS he was able to walk 3 metres with a rollator and assistance of two physiotherapists.

IV

Karavatas SG,36

2005USA

Case report(N.=1)

To illustrate the role of neurodevelopment sequencing in the physical therapy management of a geriatric patient with GBS

Inpatient rehabilitation for 2 months followed by home physical therapy programme, employing neurodevelopment-sequence positioning and evaluation by occupational therapists

– After two months of home physical therapy following improvements were noticed: – increased strength bilaterally (upper extremities, knee extension and flexion, ankle); – improved in bed mobility, all transfers, wheel chair mobility and home exercise program; – improved balance with walker; – improved in all ADLs.

– After two years of continued physical therapy program: – able to return to work; – independent in ambulation on levels of and stairs without any assistive device; – still experienced difficulty with ankle control and fine hand movements.

IV

Podiatron

Bulley P,41

2003UK

Case report(N.=1)

To evaluate the effectiveness of podiatron as an adjunct to physio therapy in a patient with GBS

Podiatron- a motorised variable pitch wobble board, with control panel and hand rails, designed specifically to mobilise and strengthen the ankles, knees, hip and back

After one week: – marked improvement in the base of support, measured by the surface area of the foot in the contact with the ground: an increase of 93% on the right and 63% on the left foot;

– increased confidence in walking, balance reactions in feet and ankle during standing activities; – however, increase in activity measures was not noted.

IV

Kyphoplasty

Masala et al.,40

2004Italy

Case report(N.=1)

To evaluate the effectiveness of kyphoplasty for an unremitting pain in person with GBS

Percutaneous kyphoplasty – Kyphoplasty provided swift midline back pain relief associated with an evident augmentation in the stability and in the vertebral body’s height.

– No complications were observed. – Due to the rapid pain relief, a rehabilitation programme was promptly undertaken with a good improvement of the disability score (FIM score).

IV

TENS

Bokhari and Zahid,59

2010Pakistan

Case report(N.=2)

To evaluate the effectiveness of TENS TENS and acupuncture – Both acupuncture and TENS contributed in marked improvement in: – Function: relieve muscle stiffness, increase motor power (increase muscle mass, improved muscle tone and force of contraction).

– Reduction in symptoms (pain).

IV

*Evidence categorised according to study design using evidence defined by the National Health and Medical Research Council (NHMRC) programme for intervention studies.23 ADLs: activities of daily living; BI: Barthel Index; CIDP: chronic inflammatory demyelinating polyneuropathy; DASS: Depression Anxiety Stress Scale; ESS: Environmental Status Scale; FIM: Functional Independent Measure; GBS: Guillain-Barré syndrome; HAS: Handicap Assessment Scale; HDS: Hughes Disability Scale; HRQoL: health-related quality of; LOS: length of stay; MBI: Modified Barthel Index scores; MRS: Modified Rankin Scale; N.= total number; NPH: Nottingham Health Profile; PIPP: Perceived Impact of Problem Profile; QoL: Quality of life; ROM: range of motion; TENS: transcutaneous electro neuro stimulation; USA: United States of America; UK: United Kingdom.

Table �IV.—�Follows from previous page.

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t is

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o do

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Phyciacal therapy/exercise

El Mhandi et al.,33

2007France

Prospective cohort study without controls (N.=6)

To assess the recovery in muscle strength and functional capacities in subjects with GBS for 18 months after onset

Individualized physical therapy programme based on muscular reinforcement and active mobilization (average 2-3 weekly sessions)

– At six months, manual muscle testing and functional independence motor total scores were close to normal levels; and at 18 months, all patients satisfied the criteria for a full recovery.

– Compared to the matched healthy controls, isometric and isokinetic strength increased significantly during the first six months (P<0.01), though muscle strength increased less rapidly (P<0.05) between 6 and 18 months.

– There was a significant negative correlation between plateau period duration and knee extensors, elbow flexors muscles strength recovery (P=0.05).

III-3

Garssen et al.,34

2004Netherlands

Prospective cohort study without controls(N.=20)

To investigate feasibility and effect of bicycle training programme on fatigue severity, physical fitness, muscle strength, functional outcome, anxiety and depression, handicap, and QoL

Structured 12-week bicycle exercise training programme

– Bicycle training was well tolerated by the participants. – Significant beneficial effect was noted on physical fitness, functional outcome, and QoL. – There was a significant improvement in the post-intervention fatigue score (decreased by 20%, P=0.001). – Majority of the participants (80%) were motivated to continue with regular training activities.

III-3

Bussmann et al.,35

2007Netherlamds

Case series (N.=20, including 6 with CIDP)

To explore the effects of physical exercise in severely fatigued patients with GBS and CIDP and to clarify the mutual relationships between various domains: physical fitness, fatigue, objectively measured actual mobility, perceived physical functioning, and perceived mental functioning

3 supervised cycle training sessions per week, for 12 weeks period

– Physical exercise resulted in improved fitness, however this did not influence in changes in fatigue, actual mobility and perceived functioning.

– Significant relationships were found between the domains: perceived mental functioning and actual mobility, perceived mental functioning and perceived physical functioning, and between fatigue and perceived physical functioning.

IV

Tuckey and Greenwood,39

2004UK

Case report(N.=1)

To evaluate the effectiveness of partial body weight support (PBwS) during remobilisation after severe GBS

Partial body weight support (Biodex unweighting support system), which makes possible to calibrate the percentage of bodyweight supported and can be used either over a treadmill or on the ground

– PBwS enabled the patient to practise walking. – Between 30-38 weeks post-onset of GBS patient was able to walk with gradually reducing PBwS at a time when he was unable even to stand without PBwS except in an electric standing frame.

– PBwS enabled patient to start task-specific gait retraining eight weeks before it would otherwise have been possible. – At 38 weeks without PBwS he walked 15 metres with a pulpit frame and the assistance of two therapists, and was managing to walk 110 metres on the treadmill with 30 kg PBwS

– At 42 weeks without PBwS he was able to walk 3 metres with a rollator and assistance of two physiotherapists.

IV

Karavatas SG,36

2005USA

Case report(N.=1)

To illustrate the role of neurodevelopment sequencing in the physical therapy management of a geriatric patient with GBS

Inpatient rehabilitation for 2 months followed by home physical therapy programme, employing neurodevelopment-sequence positioning and evaluation by occupational therapists

– After two months of home physical therapy following improvements were noticed: – increased strength bilaterally (upper extremities, knee extension and flexion, ankle); – improved in bed mobility, all transfers, wheel chair mobility and home exercise program; – improved balance with walker; – improved in all ADLs.

– After two years of continued physical therapy program: – able to return to work; – independent in ambulation on levels of and stairs without any assistive device; – still experienced difficulty with ankle control and fine hand movements.

IV

Podiatron

Bulley P,41

2003UK

Case report(N.=1)

To evaluate the effectiveness of podiatron as an adjunct to physio therapy in a patient with GBS

Podiatron- a motorised variable pitch wobble board, with control panel and hand rails, designed specifically to mobilise and strengthen the ankles, knees, hip and back

After one week: – marked improvement in the base of support, measured by the surface area of the foot in the contact with the ground: an increase of 93% on the right and 63% on the left foot;

– increased confidence in walking, balance reactions in feet and ankle during standing activities; – however, increase in activity measures was not noted.

IV

Kyphoplasty

Masala et al.,40

2004Italy

Case report(N.=1)

To evaluate the effectiveness of kyphoplasty for an unremitting pain in person with GBS

Percutaneous kyphoplasty – Kyphoplasty provided swift midline back pain relief associated with an evident augmentation in the stability and in the vertebral body’s height.

– No complications were observed. – Due to the rapid pain relief, a rehabilitation programme was promptly undertaken with a good improvement of the disability score (FIM score).

IV

TENS

Bokhari and Zahid,59

2010Pakistan

Case report(N.=2)

To evaluate the effectiveness of TENS TENS and acupuncture – Both acupuncture and TENS contributed in marked improvement in: – Function: relieve muscle stiffness, increase motor power (increase muscle mass, improved muscle tone and force of contraction).

– Reduction in symptoms (pain).

IV

*Evidence categorised according to study design using evidence defined by the National Health and Medical Research Council (NHMRC) programme for intervention studies.23 ADLs: activities of daily living; BI: Barthel Index; CIDP: chronic inflammatory demyelinating polyneuropathy; DASS: Depression Anxiety Stress Scale; ESS: Environmental Status Scale; FIM: Functional Independent Measure; GBS: Guillain-Barré syndrome; HAS: Handicap Assessment Scale; HDS: Hughes Disability Scale; HRQoL: health-related quality of; LOS: length of stay; MBI: Modified Barthel Index scores; MRS: Modified Rankin Scale; N.= total number; NPH: Nottingham Health Profile; PIPP: Perceived Impact of Problem Profile; QoL: Quality of life; ROM: range of motion; TENS: transcutaneous electro neuro stimulation; USA: United States of America; UK: United Kingdom.

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for personal, domestic and community tasks to pro-mote activities that facilitate functional self-care.5, 26,

29, 50 Introduction of recreational therapy may also support a patient’s adjustment to disability and im-prove social integration in community activities.50

Speech therapy

Cranial nerve involvement is found in most severe cases of GBS, which can lead to various complica-tions such as dysphagia and dysarthria.49 These pa-tients need a speech therapy programme to promote speech and safe swallowing skills, including pre-vention of aspiration and choking.49, 50 These pro-grammes focus on proper positioning, head control, oral motor coordination, and conscious swallowing technique (thicken fluids progressively depending on patient response). An alternative communication strategy may be required for ventilator-dependent patients. In patients with tracheostomies voicing/learning strategies may be implemented.50

Nutritional interventions

Malnutrition in patient with GBS can be caused due to immobility, decreased gastric motility, dysphagia and psychological symptoms (such as depression).51 Routine assessment of the nutritional status by treat-ing team and dietician is important.52 In acute stage most patients lose weight and are more prone to mal-nutrition,51 and may require enteric or parenteral nu-trition and high protein, high-energy enteral diets.52, 53

Cognitive and psychological interventions

Cognitive problems have been reported in pa-tients with GBS, especially in acute phase and in those with extended ICU stay.5, 16, 49 Anxiety and fear may accompany depression, which is to be expected because of the sudden onset of symptoms in these persons who are in relatively good health. In more severe patients (in intensive care settings) psychotic symptoms (hallucinations, delusions, and incoher-ence) have been reported requiring early cognitive screening.48 Appropriate interventions may include: good communication with patients and/or their fam-ily regarding prognosis and treatment plan, involve-ment in decision making and early counselling from expertise.5, 49, 51 Pastoral care can be beneficial for anxious and stressed patients/families.52

regain greater antigravity strength, more aggres-sive strengthening exercises can be applied.43 Over-working muscles in patients with peripheral nerve involvement can lead to paradoxical weakening.44 Patients with GBS can develop tightness of muscles that span two joints, rather than joint contractures; stretching programmes (e.g., hamstrings, gastrocne-mius) can alleviate this problem.5, 13

Transcutaneous electrical nerve stimulation.—Transcutaneous electrical nerve stimulation (TENS) is effective in reducing pain in other neurological conditions such as stroke, multiple sclerosis, arthri-tis.45-47 There is, however, conflicting evidence in re-gards to the beneficial effect of TENS in person with GBS. Evidence from two case reports suggests that application of TENS may be an effective treatment for the pain of peripheral neuropathy.45, 48 However, the authors concluded that further research is need-ed to support the use of TENS in the routine man-agement of pain in GBS.

Orthoses and ambulatory aids.—A high propor-tion of persons with GBS experience mobility prob-lems due to various GBS related symptoms (muscle weakness, paralysis, balance impairment, fatigue), which require use of assistive devices.26 The op-tions for mobility assistive devices vary from ankle foot orthoses, canes, crutches and walkers to power wheelchairs.26 These devices should be prescribed for proper positioning and optimising residual mo-tor function. Selection of a particular device should be determined by the patients’ strength, stability, coordination, cardiovascular capacity and cognitive status.13, 26 Patients with prolonged residual weak-ness of calf, and most commonly, anterior compart-ment musculature, benefit from ankle-foot orthosis (AFO), shoes with a broadened heel and good sta-bilization around the ankle joint.26, 49

Occupational and recreational therapy

Although majority of patients with GBS have a good functional recovery, many may continue to have a more prolonged neurologic deficits, subse-quently limiting their function at home, work, and during leisure activities. Occupational therapy fo-cuses on restoration and maintenance of functional independence skills in everyday activities in those with continued functional limitations.5, 50 Occupa-tional therapy includes: task reacquisition, use of adaptive equipment, modification of environment

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Discussion

This review provides an evidence-based over-view of the effectiveness of rehabilitation inter-vention in persons with GBS. Our comprehensive search found a limited number of robust, methodo-logically strong studies evaluating the effectiveness of rehabilitation intervention. There is “good” evi-dence in favour of MD rehabilitation (ambulatory) in producing longer term gains at the levels of ac-tivity (disability) and participation in persons with GBS. There is “satisfactory” evidence for inpatient MD rehabilitation followed by ambulatory care in improving function over a longer period; and for physical therapy. For all other rehabilitation inter-ventions, no clear favourable effects of treatment were found.

A number of narrative reviews addressed the re-habilitation approaches and described various inter-ventions used in GBS. The ‘best’ evidence to date for most uni-disciplinary rehabilitation interventions is limited and/or poor and based upon “low quality” observational studies or adopted from other neu-rological conditions. Findings from existing studies are inconclusive and adequate descriptions of the content of rehabilitation intervention are often lack-ing. Difficulties in assimilation of data are further compounded by the diversity of outcome measures used.

These conclusions are tentative, and the gap in current research should not be interpreted as inef-fectiveness of rehabilitative intervention in persons with GBS.

Limitations of the study

Rehabilitation research, including GBS is chal-lenging.58 Only one RCT, one SR and few poor quality observational studies were identified in this review. This limited a quantitative analysis for best-evidence synthesis. At present, there is paucity of in-formation on effectiveness of various rehabilitation interventions in GBS and what comprises “black box of rehabilitation” (therapy intensity, duration, modalities). More evidence is needed to guide exer-cise prescription (such as strengthening, stretching, aerobic/endurance exercises) and use of assistive technology.

Further understanding of bowel, bladder, sexuali-ty and psychosocial issues is needed. Key areas such

Interventions for respiratory complications

GBS is the most common neuromuscular cause of respiratory failure requiring ventilatory support.54 Respiratory dysfunction is encountered by almost one third of GBS patients, which can lead to se-rious complications.6, 25 The common respiratory complications in the rehabilitation setting include: incomplete respiratory recovery including chronic obstructive pulmonary disease, restrictive respira-tory disease (pulmonary scarring, pneumonia), and trachitis from chronic intubation and respiratory muscle insufficiency.55 Sleep hypercapnia and hy-poxia, which worsens during sleep can be the re-sult of restrictive pulmonary function.54 Night time saturation records with pulse oximeter and bilevel positive airway pressure (BiPAP) may be indicated for these patients.5 Physical therapy measures (chest percussion, breathing exercises, resistive inspiratory training) may be required to clear respiratory secre-tions to reduce the work of breathing.5, 13 Special weaning protocol to prevent over fatigue of respira-tory muscles can be recommended for more severe patients with tracheostomy. Patients with cranial nerve involvement need extra monitoring as they are more prone to the respiratory dysfunction.5, 13 Patients should be encouraged to cease smoking.5

Bladder/Bowel intervention (Level of evidence: Nar-rative review)

There are reports of lower motor neuron dysfunc-tion of bowel and bladder in patients with GBS.26 Bladder areflexia, disturbed bladder sensation and non-relaxing urethral sphincter are common findings in these patients, causing symptoms such as voiding difficulty, urinary retention, frequency, and urge in-continence.56, 57 These symptoms can be effectively managed with an individualised management pro-gramme, which include timed voiding, intermittent catheterization and anticholinergic medication, to achieve best QoL for these patients.42 women with stress leakage and mixed urinary incontinence can also benefit from pelvic floor muscle training.42, 50 Biofeedback or electrical stimulation, are also com-monly used with pelvic floor training as adjuncts.50

Similarly, bowel symptoms (constipation) may be common in early stage of GBS due to immobilisa-tion and/or medications. Effective bowel manage-ment programme includes an appropriate diet, ade-quate fluids, scheduled bowel care, and laxatives.6, 42

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Key messages

— There is “good” evidence to support ambula-tory (outpatient) MD high intensity rehabilitation in producing long-term gains up to 12 months at the levels of activity (disability) and participation in pa-tients with GBS in the later stage of recovery. [Level of evidence: II]

— There is “satisfactory” evidence to support in-patient MD rehabilitation followed by ambulatory (outpatient) care in producing significant functional recovery for longer period (up to 1 year). [Level of evidence: III]

— There is “satisfactory” evidence to support physical therapy/exercise in preventing joint contrac-tures and reducing muscle strength loss, to produce gains at the levels of activity (disability) in patients with GBS. [Level of evidence: III-2-IV]

— There is “poor” evidence to support TENS in reducing pain and other symptoms in patients with GBS. [Level of evidence: IV]

— There is anecdotal evidence to support the ef-fectiveness of orthotics and mobility/assistive devices in improving function or quality of life in patients with GBS. [Level of evidence: not applicable (narra-tive review)]

— There is anecdotal evidence to support effec-tiveness of occupational therapy in improving ADLs or quality of life in patients with GBS. [Level of evi-dence: not applicable (narrative review)]

— There is anecdotal evidence to support the effectiveness of speech therapy in improving swal-lowing function and communication in patients with GBS. [Level of evidence: not applicable (narrative re-view)]

— There is anecdotal evidence to support effec-tiveness of nutritional intervention in improving gen-eral status and function in patients with GBS. [Level of evidence: not applicable (narrative review)]

— There is anecdotal evidence to support the ef-fectiveness of orthotics and mobility/assistive devices in improving function or quality of life in patients with GBS. [Level of evidence: not applicable (narra-tive review)]

— There is anecdotal evidence to support the effectiveness of interventions in preventing and/or reducing respiratory complication or for improving respiratory function or quality of life in patients with

as cost-effectiveness of rehabilitative management, and neuropsychological sequelae over longer pe-riod following GBS (such as mood and work-related issues) have yet to be addressed. Further research is also needed into appropriate study designs; out-come measurement and evaluation of optimal set-tings, type and frequency of rehabilitation interven-tion for these persons. The care interface between acute and subacute settings that address needs of patients (and their caregiver) over a longer term should be explored. International guidelines incor-porating evidence-based practice in GBS rehabilita-tion need further development to improve clinical care and practice.

Hence, recommendations for future research in-clude:

1) the need for high quality studies (RCTs, CCTs) and other designs, which assess the effectiveness of specific rehabilitation interventions (components, intensity, frequency, settings). Clinical practice trials can supplement information obtained from RCTs, as they can acquire prospective and retrospective data without disrupting the natural milieu of treatment. Cost effectiveness of such programmes need explo-ration;

2) the development of appropriate, reliable and valid outcome measures, which reflect domains of the International Classification of Functioning and Health (ICF), and a consensus on a core set of meas-urement of outcomes in GBS trials;20

3) the collection of longitudinal data for long-term care needs (especially psychological care), which include issues related to aging with disabilities and cumulative impact of disabilities over time.

Conclusions

GBS is a complex and challenging condition. This paper presents an overview of current evidence for the effectiveness of rehabilitation intervention in persons with GBS. Integrated holistic multidiscipli-nary rehabilitative care of these persons is recom-mended to address various medical, physical and psychological issues. Methodologically robust trials are needed to build evidence based rehabilitation practices to evaluate outcomes for improved care. Further, development of clinical practice guidelines for the longer-term management of these persons is needed.

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