neurological research and practice

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Neurological research and practice, latest issues, neurological research and practice 1/2024, neurological research and practice 1/2023, neurological research and practice 1/2022, neurological research and practice 1/2021, neurological research and practice 1/2020, neurological research and practice 1/2019.

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Neurological Research and Practice , official journal of the German Neurological Society, is an international publication with a broad scope reflecting all clinical, translational and basic research aspects of neurology and neuroscience. Neurological Research and Practice provides a forum for clinicians and scientists with an interest in all areas of neurology including, but not limited to, genetics, vascular diseases and critical care, disorders of the spine, movement disorders, neuroimmunology, infections, oncology, epilepsy, neuroimaging and neuroradiology, neurodevelopment and degeneration. The journal will publish research articles, reviews, clinical trial protocols, standard operating procedures, letters to the editor and guidelines.

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Ausgabe 1/2022

Inhalt (62 artikel), therapy development for spinal muscular atrophy: perspectives for muscular dystrophies and neurodegenerative disorders.

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Carriers of POLG1 variants require investigations for multisystem disease and for mtDNA variations

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S. Latarnik, J. Stahl, S. Vossel, C. Grefkes, G. R. Fink, P. H. Weiss

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Long-term efficacy with deep brain stimulation of the globus pallidus internus in cervical dystonia: a retrospective monocentric study

Clemens Jacksch, Kirsten E. Zeuner, Ann-Kristin Helmers, Karsten Witt, Günther Deuschl, Steffen Paschen

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Daniel Richter, Andreas Ebert, Lisa Mazul-Wach, Quirin Ruland, Jeyanthan Charles-James, Ralf Gold, Georgios Tsivgoulis, Georg Juckel, Christos Krogias

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Aktuelle Ausgaben

Neurological research and practice 1/2024, neurological research and practice 1/2023, neurological research and practice 1/2022, neurological research and practice 1/2021, neurological research and practice 1/2020, neurological research and practice 1/2019.

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ORIGINAL RESEARCH article

Interrater reliability of the fugl-meyer motor assessment in stroke patients: a quality management project within the estrel study.

• 1 Neurorehabilitation and Neurology, University Department of Geriatric Medicine FELIX PLATTER, University of Basel, Basel, Switzerland
• 2 Department of Health Professions, Bern University of Applied Sciences, Bern, Switzerland
• 3 Division of Vascular Neurology and Neurorehabilitation, Department of Neurology, University of Zurich and University Hospital Zurich, Zurich, Switzerland
• 4 Department of Neurology and Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland
• 5 Cereneo Center of Neurology and Rehabilitation, Zurich, Switzerland
• 6 Valens Clinics, Reha Center Triemli, Vitznau, Switzerland

Introduction: The Fugl-Meyer Motor Assessment (FMMA) is recommended for evaluating stroke motor recovery in clinical practice and research. However, its widespread use requires refined reliability data, particularly across different health professions. We therefore investigated the interrater reliability of the FMMA scored by a physical therapist and a physician using video recordings of stroke patients.

Methods: The FMMA videos of 50 individuals 3 months post stroke (28 females, mean age 71.64 years, median National Institutes of Health Stroke Scale score 3.00) participating in the ESTREL trial (Enhancement of Stroke Rehabilitation with Levodopa: a randomized placebo-controlled trial) were independently scored by two experienced assessors (i.e., a physical therapist and a physician) with specific training to ensure consistency. As primary endpoint, the interrater reliability was calculated for the total scores of the entire FMMA and the total scores of the FMMA for the upper and lower extremities using intraclass correlation coefficients (ICC). In addition, Spearman’s rank order correlation coefficients (Spearman’s rho) were calculated for the total score and subscale levels. Secondary endpoints included the FMMA item scores using percentage agreement, weighted Cohen’s kappa coefficients, and Gwet’s AC1/AC2 coefficients.

Results: ICCs were 0.98 (95% confidence intervals (CI) 0.96–0.99) for the total scores of the entire FMMA, 0.98 (95% CI 0.96–0.99) for the total scores of the FMMA for the upper extremity, and 0.85 (95% CI 0.70–0.92) for the total scores of the FMMA for the lower extremity. Spearman’s rho ranged from 0.61 to 0.94 for total and subscale scores. The interrater reliability at the item level of the FMMA showed (i) percentage agreement values with a median of 77% (range 44–100%), (ii) weighted Cohen’s kappa coefficients with a median of 0.69 (range 0.00–0.98) and (iii) Gwet’s AC1/AC2 coefficients with a median of 0.84 (range 0.42–0.98).

Discussion and conclusion: The FMMA appears to be a highly reliable measuring instrument at the overall score level for assessors from different health professions. The FMMA total scores seem to be suitable for the quantitative measurement of stroke recovery in both clinical practice and research, although there is potential for improvement at the item level.

Introduction

Motor impairment is one of the most important disabilities associated with stroke and can significantly affect the quality of life ( 1 ). Muscle weakness, abnormal synergy, and spasticity are among the motor deficits commonly assessed in stroke patients ( 2 ). Considering the repair processes, measuring motor recovery after stroke is very important. The Fugl-Meyer Motor Assessment (FMMA) ( 3 ) is strongly recommended as a clinical and research tool for the evaluation of changes in motor impairment after stroke ( 4 ). It was a key component of the assessment recommendations for improving the methodology of adult rehabilitation and recovery trials ( 5 ) and clinical motor rehabilitation ( 6 ), which should be repeated at different measurement time points. The inclusion of the upper extremity FMMA (FMMA-UE) in further recommendations for outcome measurement after stroke has confirmed its importance ( 7 , 8 ).

The maximum total score per side is 66 points for the FMMA-UE and 34 points for the lower extremity FMMA (FMMA-LE) ( 4 ). The FMMA items are rated on an ordinal scale with the scores 0 = cannot perform, 1 = performs partially and 2 = performs fully ( 4 ). The practical implementation of the test and the assessment of its individual items require standardized, sound training as well as routine. These aspects can be promoted by a uniform test version in the different languages of the respective countries of application. Upon completion of the present project, standardized FMMA test forms translated into more than 10 different languages were available [e.g., at https://www.gu.se/en/neuroscience-physiology/fugl-meyer-assessment ( 9 )]. However, to the best of our knowledge, no standardized, validated German version of the test is currently available. Therefore, we developed an adapted German version of the assessment, based on the original article and protocols of the University of Gothenburg ( 3 , 10 , 11 ). The corresponding assessment forms can be found in the Supplementary Table S1 . The interprofessional application of this German version of the FMMA into clinical trials requires good psychometric properties in terms of the validation process.

A high interrater reliability of the German version of the FMMA across different health professions is essential for the use of the assessment in clinical studies, but also for its application in daily rehabilitation practice. The English version of the FMMA showed excellent intra- and interrater reliability ( 4 ). Platz et al. ( 12 ) found a very high interrater reliability of the FMMA-UE with intraclass correlation coefficients (ICC) based on video recordings. In the Sullivan et al. ( 13 ) study, interrater agreement between expert and therapist raters using video recordings was high for the FMMA total scores with an ICC value of 0.98 as well as for total scores of the FMMA-UE with 0.99 and moderate to high for the FMMA-LE total scores with 0.91. Based in part on the strong evidence for validity, reliability, responsiveness, and clinical utility, the FMMA-UE was incorporated into the core set of European evidence-based recommendations for Clinical Assessment of Upper Limb In Neurorehabilitation (CAULIN) ( 7 ).

In this context, refined reliability data and the availability of transculturally adapted, validated FMMA versions in different languages are even more important. Investigating the interrater reliability of new FMMA versions using sufficiently large samples is a relevant component in this regard. Therefore, we aimed to investigate (i) the interrater reliability of the German FMMA across health professions and (ii) the comparability of the psychometric properties of the German FMMA with those of the English version.

Materials and methods

Project objectives and design.

The aim of this research project was to study the interrater reliability of the German version of the FMMA in terms of its consistent and accurate application across health professions. The FMMA is used in the ongoing Swiss multicentre ESTREL trial (Enhancement of Stroke Rehabilitation with Levodopa: a randomized placebo-controlled trial, BASEC-number 2018–02021, ClinicalTrials.gov NCT03735901) ( 14 ), in which the current reliability study with a cross-sectional design was embedded.

Study population and procedure

All patients in this study had a video recorded FMMA at their regular three-month visit as part of their participation in ESTREL ( 14 , 15 ). In brief, ESTREL investigates whether Levodopa, compared to placebo, given in addition to standardized rehabilitation based on the principles of motor learning, is associated with a patient-relevant enhancement of functional recovery in acute ischemic or haemorrhagic stroke patients, as measured by the FMMA after 3 months ( 14 , 15 ).

The present project followed the Guidelines for Reporting Reliability and Agreement Studies (GRRAS) ( 16 ). As a preparatory step, an extensive literature research on relevant FMMA publications in the English-speaking world was conducted. After the selection of adequate reference literature, different FMMA versions were analyzed in detail and their contents were precisely compared. Between December 2019 and May 2021, FMMA video recordings of the three-month visit of ESTREL stroke patients were performed at the two best recruiting centres, Basel and Zurich, Switzerland. The FMMA was applied in an outpatient visit setting, in most cases by the first author (KW).

The sampling method of the recordings was consecutive, following a standardized procedure. Eligibility criteria: We took the first 72 available FMMA videos from ESTREL participants who were eligible for the trial ( 14 ). Of these, 62 videos were identified in Basel and 10 in Zurich. The first author (KW) performed a quality check of all collected videos based on the criteria of (i) completeness, (ii) visibility of the entire examination, and (iii) potential source of bias. Video recordings were excluded, if (a) the FMMA was incomplete, (b) a FMMA subscale was not fully visible, and (c) the evaluation sheet with the FMMA ratings was visible on the video. In addition, recordings were excluded if one of the assessors of the videos was the FMMA examiner being videotaped. A flowchart of the video selection process is presented in Figure 1 .

Figure 1 . Flow chart of the selection process for FMMA video recordings. FMMA, Fugl-Meyer Motor Assessment; n, number of subjects.

Independent assessors

Two independent assessors – one from each participating centre – rated the FMMA videos. Rating was limited to the hemiparetic side in each case. The assessors consisted of one research physician (LM) and one research physiotherapist (AS) from the two different centres, each with a master’s degree and clinical experience – who met the following criteria: First, both assessors had participated at least twice in a standardized, four-hour in-person FMMA training course by an FMMA expert (JH), based on the German version of the FMMA (see Figure 2 , FMMA training). Second, both assessors had applied the German version at least 50 times on stroke patients in a standardized setting.

Figure 2 . Example illustration from FMMA training for assessors: FMMA-UE. FMMA-UE, Fugl-Meyer motor assessment upper extremity.

The assessors scored the videos separately in space and time, and independently of each other and other study personnel. The scores were directly entered in coded electronic case report forms (eCRF) of the German version of the FMMA within the secure web application REDCap (Research Electronic Data Capture) ( 17 ). Regarding clinical information, the assessors were unaware of the initial stroke severity, including the FMMA scores at baseline, but were not blinded to the medical history of the subjects in the video recordings. Both assessors had the same access to on-site training and additional video tutorials for recapitulation. They were given additional guidance and explanation on how to proceed in special situations where FMMA items could not be completed for non-stroke-related reasons (e.g., due to pain) or where items were incomplete on video. The flow chart of the study procedure can be found in Figure 3 .

Figure 3 . Flow chart of the study procedure. FMMA, Fugl-Meyer Motor assessment.

Data recording and confidentiality

The videos were recorded with a GoPro camera, GoPro Incorporation (San Mateo, California, US). Camera positions (heights, distances) were exactly defined in written form for the FMMA-UE and the FMMA-LE and are presented in the Supplementary Figure S1 . The storage of all health-related personal data was protected by appropriate operational and organizational measures in accordance with Article 18 of the Ordinance on Clinical Trials in Human Research of the Swiss Confederation ( 18 ).

The informed consent form for the ESTREL trial specifies that the FMMA tests may only be recorded and used for internal research purposes in order to conduct a thorough evaluation.

Statistical reliability analysis

A sample size of 50 subjects was recommended for reliability studies in order to reasonably determine kappa values ( 19 ). In our project, we followed this recommendation, as well as appropriate reference studies that included between 10 and 60 individuals after stroke in their reliability analyses ( 12 , 13 , 20 – 26 ).

Our primary endpoint was the interrater reliability of the FMMA, calculated for the total scores of the entire FMMA and the total scores of the FMMA for the affected extremities using ICCs with the corresponding 95% confidence intervals (CI). The following ICC form fitted the model best: Two-way mixed effects, absolute agreement, multiple raters/measurements ( 27 , 28 ). ICC values were also calculated for the FMMA subscales, as these parameters were recommended for use with continuous variables ( 19 ). For comparison with the reference literature, ICCs were calculated for all FMMA subscales. Since it is questionable whether the ICC – as a parameter for continuous variables ( 19 ) – is suitable for variables with few levels, the ICC was not considered as the only parameter for the coordination subscales (three items/0–6 levels) of the FMMA and for the wrist (five items/0–10 levels) and hand (seven items/0–14) subscales of the FMMA-UE. For these subscales, weighted Cohen’s kappa values with associated CIs were calculated. Since the data were non-parametric, Spearman’s rank-order correlation coefficients (Spearman’s rho values) with appropriate p -values and 95% CI were calculated to document the strength of association for total and subscale evaluations between assessor 1 and assessor 2.

Several statistical procedures formed the secondary endpoints for assessing the reliability of the FMMA at the item level: (i) Percentage agreement values between the two ratings were calculated for all 50 FMMA individual tasks of the affected extremities. (ii) Weighted Cohen’s kappa ( 29 , 30 ) values and corresponding 95% CI were obtained from the FMMA ordinal variables. (iii) Gwet’s AC1/AC2 coefficients with corresponding 95% CIs were calculated at the item level in addition to the weighted Cohen’s kappa values.

Statistical procedures to determine all end points were performed using RStudio software, version 1.2.1335.

Evaluation of parameters

Reliability parameters were categorized according to appropriate classifications (see Supplementary Tables S2, S3 ): We applied the 95% CIs of the ICC estimates for interpretation instead of the ICC estimates themselves ( 27 ) and used the Landis and Koch ( 31 ) classification for the weighted Cohen’s kappa and the Gwet’s AC1/AC2 values to compare the results of the German FMMA with those of previously published studies.

Fifty video recordings were eligible to study the interrater reliability of the German FMMA version ( Figure 1 ). There were no missing data that affected the statistical analysis.

Patient characteristics

50 individuals with stroke were recorded 3 months ±14 days after randomization in the ESTREL trial. 28 of the participants were female, the mean age was 71.64 years, and the median National Institutes of Health Stroke Scale (NIHSS) score was 3.00. All patient demographic and clinical characteristics are presented in Table 1 .

Table 1 . Patient demographic and clinical characteristics.

Descriptive findings of the Fugl-Meyer Motor assessment

Between June and September 2021, 50 FMMA ratings were carried out by both assessors. The difference in median total scores between assessors was less than three points for the FMMA-UE and one point for the FMMA-LE. The median values with the corresponding first and third quantiles of the two assessors’ total FMMA scores are shown in Table 2 .

Table 2 . FMMA median and quantile values of the two assessors.

Primary endpoint

All interrater reliability parameters at the overall score and subscale levels of the FMMA are shown in Table 3 .

Table 3 . Interrater reliability parameters of the German version of the FMMA at the overall score level.

For all total scores (FMMA-UE, FMMA-LE and entire FMMA) as well as for the proximal part subscale of the FMMA-UE and the hip, knee, ankle subscale of the FMMA-LE, the ICC values were between 0.80 (95% CI 0.64–0.88) for volitional movement within flexor and extensor synergies of the lower extremity and 0.98 (95% CI 0.96–0.99) for the total scores of the FMMA-UE. The total scores of the entire FMMA were very similar at 0.98 (95% CI 0.96–0.99). Using Koo and Li′s ( 27 ) classification for the 95% CI of the ICC values, the reliability of the meaningful subscales as well as that of the total scores (values written bold in Table 3 ) was classified as moderate to excellent.

Weighted Cohen’s kappa values ranged from 0.62 (95% CI 0.42–0.83) for the coordination subscales of the FMMA-LE to 0.91 (95% CI 0.91–0.91) for the hand subscales of the FMMA-UE. Using Landis & Koch (1979) ( 31 ) benchmarking for kappa statistics, the strength of agreement was found to be moderate to almost perfect.

The Spearman’s rank-order correlation coefficients for the total score and subscale levels ranged from 0.61 to 0.94 (median 0.91), with the lowest value for the hip, knee, ankle subscales of the FMMA-LE (values <0.7). The highest values were obtained for the FMMA-UE total scores, the total scores of the entire FMMA, and the wrist, hand, and the coordination subscales of the FMMA-UE (values >0.9). All p -values of Spearman’s rank-order correlation coefficients were smaller than 0.001.

Secondary endpoints

All item-based interrater reliability parameters of the German version of the FMMA-UE are summarized in Table 4 and those of the FMMA-LE in Table 5 . A graphical representation comparing all three item-level measures of the FMMA is shown in Figure 4 .

Table 4 . Item-based interrater reliability parameters of the German version of the FMMA-UE.

Table 5 . Item-based interrater reliability parameters of the German version of the FMMA-LE.

Figure 4 . Graphical representation comparing percentage agreement, weighted Cohen’s kappa, and Gwet’s AC2 for each item. The items on light blue background are part of the FMMA-LE, those on light red of the FMMA-UE. Individual measurement points overlap for item Ib of the FMMA-LE and items Ia, Ib, VIa, and VIIIc of the FMMA-UE. FMMA-LE, Fugl-Meyer Motor assessment lower extremity; FMMA-UE, Fugl-Meyer Motor assessment upper extremity; gwet, Gwet’s AC1/AC2 coefficient; kappa, weighted Cohen’s kappa coefficient; pagree, percentage agreement.

Most of the assessor agreements were above 0.75 for most of the items. The three different statistical parameters (percentage agreement, weighted Cohen’s kappa coefficients, Gwet’s AC1/AC2 coefficients) shown in the graph were far apart for some items, indicating a high heterogeneity, while they were close for others. It can also be seen that the parameter distances were generally larger for the lower extremity items than for the upper extremity items.

Percentage agreement values for upper extremity items ranged from 44 to 98% (median 77%), with the highest data for reflex activities (values >95%) and the lowest for one component each of the flexor synergy and the coordination subscale (values <50%). Agreement values for the FMMA-LE were generally similar to those of the FMMA-UE and ranged from 44 to 100%. The highest agreement was found for the presence or absence as well as the quality of reflex activity (values >95%) and the lowest for two components of the coordination subscale (values <50%).

As presented in Table 4 , weighted Cohen’s kappa coefficients of the upper extremity items ranged from 0.00 (95% CI 0.00–0.00) to 0.98 (95% CI 0.98–0.98) with a median of 0.73. Based on the benchmarking of Landis & Koch (1977) ( 31 ), the strength of the agreement could be classified as slight to almost perfect. For the FMMA-LE (see Table 5 ), the lowest kappa values were 0.00 (95% CI 0.00–0.00) for item Ib. as well as for item Va. and the highest was 0.74 (95% CI 0.74–0.74) for one component of the tasks performed in a sitting position. The median was 0.47. Thus, the degree of agreement was slight to substantial.

In most cases, the Gwet’s AC1/AC2 coefficients were higher than the weighted Cohen’s kappa coefficients. Based on these Gwet’s AC1/AC2 values (median for the items of the entire FMMA 0.84, range 0.42–0.98; median for the items of the FMMA-UE 0.82, range 0.58–0.98; median for the items of the FMMA-LE 0.87, range 0.42–0.97), moderate to almost perfect agreement according to the classification of Landis and Koch (1977) ( 31 ) was found for the FMMA-UE, while it was also moderate to almost perfect for the lower extremity.

The results indicate the following key findings: (i) The total scores of the entire FMMA show excellent interrater reliability of the German FMMA version across different health professions. This makes it suitable for quantitative measurement of stroke recovery in both clinical practice and research. (ii) Interrater reliability at the item level was lower than in comparable studies with FMMA versions in other languages, leaving room for potential improvement in this area.

Interrater reliability at the overall score level

For the total scores of the entire FMMA, which includes both the FMMA-UE and FMMA-LE, the ICC was 0.98 (95% CI 0.96–0.99), which is considered excellent ( 27 ). This finding is consistent with studies that investigated the interrater reliability of the English version of the FMMA in different settings ( 12 , 13 , 26 ).

Item-level interrater reliability

The percentage agreement values in the present study, which ranged from 44 to 98% for the FMMA-UE and from 44 to 100% for the FMMA-LE, were lower than those of the Colombian Spanish version of Hernández et al. (2019, 2020) ( 24 , 25 ), which ranged from 88 to 100% for the FMMA-UE and FMMA-LE. The level of agreement for the items of the FMMA-UE and FMMA-LE in the transculutural/cross-cultural translation and validation studies was above 70% for an Italian version ( 23 ) and for a Danish version ( 22 ). Both working groups classified an agreement of ≥70% as satisfactory ( 22 , 23 ). In contrast, the agreement values for our German version were below 70% for eight items of the FMMA-UE (seven of them within the proximal part subscale) and five items of the FMMA-LE (two of them within the coordination subscale).

Particularly noticeable are the lower percentage agreement values of the respective three items from the coordination subscales of the FMMA-UE and FMMA-LE compared to the data of the above-mentioned articles. In this study, the FMMA-UE coordination item values ranged from 48 to 96% (with the lowest value for dysmetria followed by tremor) and FMMA-LE values ranged from 44 to 82%, whereas the reference studies reported FMMA-UE coordination item values of at least 80% and FMMA-LE values of at least 70% ( 22 – 25 ). These discrepancies raise the question of whether the items of the coordination subscale of the German FMMA should be defined more specifically.

Another explanation for the lower interrater reliability values at the item level in the present project could be that the assessors of the reference studies were therapists ( 22 – 25 ). In the present project the assessors consisted of a physician and a physiotherapist. At the item level, profession-specific differences in rating may well be apparent.

Implications for research and clinical practice

According to expert recommendations ( 5 , 6 , 8 ), the FMMA should be implemented as important assessment for the body function and structure domain of the International Classification of Functioning, Disability and Health (ICF) throughout the continuum of stroke care to optimize the quality of the rehabilitation pathway. The results of the present project make a small but important contribution on this way.

To ensure a consistent and uniform application of the FMMA, a clear, standardized training and refresher training structure as well as a lively exchange between assessors during the training process are of great importance. These elements are largely similar to the procedures used in our training setting. Therefore, and in line with See et al. ( 26 ), we recommend the creation of instructional videos as well as test patient videos to compare scoring as a supplement to FMMA presence training in small groups with an expert and standardized assessment forms.

Based on the proposed measures, the assessment forms of the German version of the FMMA can be further developed and the training structure can be adapted. In the future, international standardization and harmonization of FMMA protocols might be useful.

To the best of our knowledge, this is the first reliability study with a cross-sectional design at a predefined measurement time point in which two assessors evaluated the interrater reliability of a German FMMA version using video recordings of 50 individuals after stroke. Except for the studies by Hernández et al. ( 24 , 25 ) with 60 stroke patients, all selected reference studies with similar populations had smaller sample sizes ( 12 , 13 , 21 – 23 , 26 , 32 ). Furthermore, the consistency of the ICC values across different calculation methods indicated the robustness of our key findings.

The assessors of the current project belong to two different health professions (a physician and a physical therapist), which can be seen as a strength considering that the FMMA is meant to be used more widely in the future. Therefore, and for the envisioned higher acceptance of the FMMA as key motor recovery assessment tool, a high reliability across different professions is essential. Another strength was that the video recordings could be evaluated remotely, avoiding repetitions of the FMMA, which would have introduced the risk of bias due to learning effects. Furthermore, the video approach may allow centralized adjudication within the multicentre ESTREL trial and could improve the quality of future stroke recovery and rehabilitation studies.

Limitations

We are aware of the following limitations of our project. Firstly, the generalisability of the findings based on video recordings with only two assessors has not been demonstrated. A future statistical reliability analysis should incorporate the original FMMA scores from the ESTREL database obtained from real measurements at the time of videotaping in the presence of patients. In this way, the original on-site FMMA ratings might be compared with the ratings of the two assessors based on the videotaped FMMA. This would allow additional comparison of interrater reliability with that reported in the literature based on FMMA ratings in the presence of patients.

Secondly, different statistical approaches to calculating interrater reliability were described in the literature. The parallel calculation of Gwet’s AC1/AC2 coefficients for the item level of the FMMA can be considered a useful complement to the weighted Cohen-Kappa coefficients. The statistic of Gwet, in turn, is not well known because studies of interrater reliability in the current research field rarely report these coefficients. The comparability of study results is important in this context, which is why the use of Svensson’s method ( 33 ), for example, should be considered in future cross-cultural translations and adaptations. Likewise, the determination of systematic disagreement would be an interesting approach. For example, the tasks actively performed by patients with combined movement levels and directions, which are difficult to assess from only one perspective, tended to reflect more systematic inconsistencies. This was evident in some large movement tasks as well as in the evaluation of dysmetria of the FMMA-UE, but also in the standing items and coordination tasks (dysmetria and tremor) of the FMMA-LE. Thirdly, the results of our study are not necessarily applicable to populations other than stroke patients and to assessors from other health professions (e.g., study nurses).

The FMMA appears to be a highly reliable measuring instrument at the overall score level for assessors from different health professions. The FMMA total scores seem to be suitable for the quantitative measurement of stroke recovery in both clinical practice and research, although there is potential for improvement at the item level.

Data availability statement

The datasets generated for this study are available on request to the corresponding author.

Ethics statement

All participants had provided their informed consent to participate in ESTREL, in which videotaping of the FMMA is mentioned. Ethical review and approval were not required for the study on human participants in accordance with the local legislation and institutional requirements (BASEC-Nr. Req.-2020–00443). Written informed consent was obtained from the individuals for the publication of any potentially identifiable images or data included in this article.

Author contributions

KW: Writing – review & editing, Writing – original draft. AS: Writing – review & editing. LM: Writing – review & editing. JK: Writing – review & editing. CT: Writing – review & editing. AL: Writing – review & editing. JH: Writing – review & editing, Writing – original draft. SE: Writing – review & editing, Writing – original draft.

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Swiss National Science Foundation (project number 179667), and the P&K Puehringer Foundation.

Acknowledgments

We would like to thank all experts for their participation: Nathanael Lutz, Sabine Schaedelin, Jan Taeymans, and Amir Tal.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Supplementary material

The Supplementary material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fneur.2024.1335375/full#supplementary-material

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Keywords: Fugl-Meyer assessment, stroke, motor disorders, recovery, rehabilitation, reliability, training

Citation: Wiesner K, Schwarz A, Meya L, Kaufmann JE, Traenka C, Luft AR, Held JPO and Engelter S (2024) Interrater reliability of the Fugl-Meyer Motor assessment in stroke patients: a quality management project within the ESTREL study. Front. Neurol . 15:1335375. doi: 10.3389/fneur.2024.1335375

Received: 08 November 2023; Accepted: 04 March 2024; Published: 08 April 2024.

Reviewed by:

Copyright © 2024 Wiesner, Schwarz, Meya, Kaufmann, Traenka, Luft, Held and Engelter. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Karin Wiesner, [email protected]

† These authors have contributed equally to this work and share last authorship

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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Guillain-barré syndrome (GBS) with antecedent chikungunya infection: a case report and literature review

• Sreelakshmi V. 1   na1 ,
• Amrita Pattanaik   ORCID: orcid.org/0000-0002-1562-0347 1   na1 ,
• Srilatha Marate 1 ,
• Reeta S Mani 2 ,
• Aparna R. Pai 3 &
• Chiranjay Mukhopadhyay 1  

Neurological Research and Practice volume  6 , Article number:  21 ( 2024 ) Cite this article

Metrics details

Guillain-Barré Syndrome (GBS) is an autoimmune neuropathy. Antecedent infections have been seen to be significant triggering factors for developing GBS. Among them, arboviral infections are rapidly gaining importance as significant triggers, especially in the areas where they are endemic. Chikungunya, an arboviral infection that usually causes a self-limiting acute febrile illness can lead to GBS as one its severe complications. Herein, we describe a case of a 21-year-old female who presented with weakness in all four limbs and paresthesia. Nerve conduction study and cerebrospinal fluid (CSF) analysis showed axonal, demyelinating motor and sensory neuropathy with albuminocytological dissociation indicating Acute Motor and Sensory Axonal Neuropathy (AMSAN) variant of GBS. Serum IgM antibodies against ganglioside GM1 were detected. Anti-Chikungunya IgM antibodies were found in both serum and CSF samples. The patient was initiated with Intravenous Immunoglobulin (IVIG) therapy. In view of hypoxia, she was intubated and was on mechanical ventilation. After 2 weeks of being comatose, the patient gradually improved and was discharged with no sequelae.

A literature review on antecedent infections in GBS is presented alongside the case report to better understand the association of GBS with antecedent infections, especially the endemic arboviral infections like Chikungunya, Dengue and Zika. This will help in reinforcing the significance of having robust surveillance and public health control measures for infectious diseases.

Guillain-Barré Syndrome (GBS) is a rare but serious autoimmune disorder, affecting the peripheral nervous system (PNS). Highlighting the magnitude of the problem, globally, it has an annual incidence of 1–2 cases per 100,000 people [ 1 ]. However, regional differences in the incidence rate has been observed. As per the prevalence surveys done in Europe, Asia, America, and Australia, 0.4 to 4 GBS cases per 100,000 people have been reported annually [ 2 ]. In Asia, an annual incidence of 1.71, 1.82, 0.42 GBS cases per 100,000 people have been observed in China, South Korea, and Japan respectively [ 3 , 4 ]. These cases have been more frequently reported during the monsoon season in some regions [ 2 , 5 ]. However, contradicting this, in other geographical locations, studies have reported the peak of GBS cases in summer and winter, thus pointing towards a regional variation in the seasonality of the cases. Some studies also suggest that there is no discernible seasonal fluctuation [ 6 , 7 ]. Increased incidence in GBS is also observed during outbreaks and pandemics. A recent instance is the significant rise in GBS cases following the COVID-19 pandemic [ 8 , 9 , 10 ]. Although the exact cause of GBS is still unknown, it is speculated to be a post-infectious condition since 2/3rd of the patients suffer from some form of infectious disease before the neurological condition sets in [ 11 , 12 ]. Many bacterial and viral infections have been implicated in triggering the immune system against nerves, damaging it. As a consequence, weakness and tingling sensation in the extremities progressing to acute flaccid paralysis is seen [ 12 , 13 ]. Less than one-third of the patients with GBS require mechanical ventilation due to respiratory muscle weakness. A mortality rate of 1–18% has been reported in such patients [ 14 , 15 ]. Early diagnosis and treatment with intravenous immunoglobulin or plasmapheresis are effective in reducing the severity of the illness and aid in the recovery of the patients [ 12 ]. GBS is mostly a monophasic condition, but recurrence is observed in about 3–10% of the patients. It may occur at any age, however, higher incidences have been observed in adults compared to children with a predominance seen in males [ 16 , 17 ].

GBS is a heterogeneous disorder having regional variation with respect to the clinical presentation, electrophysiological subtype, and outcome [ 18 ]. The lack of definitive cause and effective treatment is a major challenge that clinicians are facing even after 100 years since the reporting of the first case of GBS. Herein, we present a clinical case of fulminant GBS with antecedent Chikungunya infection. Chikungunya infection is an acute febrile illness usually associated with rashes and arthralgia, transmitted through Aedes aegypti and Aedes albopictus mosquitoes [ 19 , 20 ]. Although meningitis, encephalitis, and GBS have been documented as consequences of a severe acute Chikungunya infection, neurological complications are uncommon [ 21 ]. Neurological complications of Chikungunya infection, including one case of GBS were first observed during the outbreak of 1964 in Madras, India [ 22 ].

The objectives of this review include: (i) reviewing the antecedent infections in GBS, (ii) illustrating the pathogenesis of GBS, (iii) describing the clinical features, and (iv) summarizing the treatment and management.

Case presentation

A 21-year-old female presented with rapid progressive weakness involving all four limbs associated with sensory symptoms in the form of paraesthesia followed by numbness. A month prior, she suffered from high-grade fever, chills, rigors with no other symptoms. There was no laboratory confirmed etiological diagnosis. No other premorbid conditions were found as well.

On initial examination, patient had respiratory distress with hypoxia, in view of which she was intubated and was put on control mode of ventilation. Neurological examination revealed tetraparesis, with paraesthesia of the extremities. There was bilateral but asymmetric facial palsy. Deep tendon reflexes were abolished. Pupils were sluggishly reactive. Routine blood examination revealed hyponatremia (126 mEq/L), anaemia with Vitamin B12 and folate deficiency, mild hypokalaemia (3.4 mmol/L), and elevated inflammatory markers. Nerve conduction study and CSF analysis identified axonal, demyelinating motor and sensory neuropathy with albuminocytological dissociation which indicated the Acute Motor Sensory Axonal Neuropathy (AMSAN) variant of GBS. Patient’s serum was positive for IgM antibodies against GM1 ganglioside; IgM antibodies against Chikungunya virus were found to be present in both serum and CSF. IgM antibodies against other prevalent arboviruses like Dengue, Zika, Japanese encephalitis virus, West Nile virus were not detected in both serum and CSF samples.

IVIG therapy (0.4 g/kg/day for 5 days) along with other supportive measures were immediately initiated in the patient. Nevertheless, she continued to deteriorate and 2 days later, ocular movements were lost with power in limbs worsening to zero. The EEG demonstrated severe encephalopathy with theta waves, suggestive of deep coma attributed to hyponatremia and sedation during intubation. She remained comatose with Glasgow Coma Scale score of 3 even after the completion of one course of IVIG therapy. Therefore, another cycle of IVIG therapy was administered. Despite a normal MRI report, a diagnosis of Bickerstaff brainstem encephalitis was considered because of the clinical picture that was presented.

After 10 days, the patient could move her lip, jaw, shoulders, proximal limbs and showed distal flickering. She was eventually removed from ventilatory support. Even with protective measures in place, due to facial weakness, exposure keratitis occurred and was managed by lid taping by the ophthalmology consultant. While intubated, the patient developed paralytic ileus for a few hours which was managed conservatively with bowel rest and intravenous fluid therapy. Physiotherapy and swallowing exercises were started along with iron, vitamin B12, and folate supplementation and continued after discharge. At discharge, she was hemodynamically stable with power of 4/5 in all four limbs, she was able to swallow semi- solids, and maintained saturation in room air.

Literature review: antecedent infections in GBS

Methodology.

We conducted the literature search through multiple search engines such as PubMed, Scopus, Medline, Google Scholar, and ScienceDirect using the search terms: “Guillain-Barré Syndrome”, “GBS”, “autoimmunity”, “antecedent infection”, “bacteria”, “viruses”, “molecular mimicry”, “arboviruses in GBS”, “Chikungunya infection in GBS”, “intravenous immunoglobulins”, “plasmapheresis”. Thereafter, the search was limited to observational and interventional studies on Guillain-Barré Syndrome with antecedent infections. Only articles published in English language were considered. Additionally, relevant studies were identified through reference analysis. The articles available from 1st January 1990 until 31st December 2023, under the above-mentioned criteria were scanned and relevant studies were included in this narrative review. The results are presented under four headings: Antecedent infections causing GBS, Pathogenesis of GBS, Clinical manifestations and Diagnosis, and Treatment and Prognosis.

In addition, all the published cases of GBS with antecedent Chikungunya were included in this literature review. Up to 31st December, 2023, nine papers were published and a total of 33 cases have been described (Table  1 ). There was no gender prevalence, and the average age of patients studied was 51.

Antecedent infections causing GBS

Though the definitive cause of GBS is still unknown, it has been noted that antecedent infections within two to four weeks were present in 2-3rd of the GBS patients before the onset of neurological symptoms [ 11 , 12 ]. A wide spectrum of infectious agents including bacteria and viruses have been reported to cause GBS. Among them, the commonest agent is the Campylobacter jejuni , a Gram-negative bacteria causing gastroenteritis which accounts for 33% of GBS cases in the western countries, and 45–60% in China and Japan [ 11 , 23 , 24 , 25 , 26 , 27 , 28 ]. Other bacteria like Mycoplasma pneumoniae and Haemophilus influenzae have also been reported to trigger GBS [ 11 , 29 ].

Several viral infections have been associated with triggering GBS and have been reported worldwide. A case-control study conducted in Netherlands in 154 GBS patients reported antecedent infections with CMV, EBV, Parainfluenza 1 virus, Influenza A, Influenza B, Adenovirus, Herpes simplex virus (HSV), Varicella zoster virus (VZV) [ 11 ]. Another study conducted in China with 150 GBS patients reported antecedent infections with Influenza A virus, Influenza B virus, Hepatitis E virus (HEV), Hepatitis A virus (HAV), Dengue virus, Cytomegalovirus (CMV), Epstein- Barr virus (EBV), Herpes simplex virus (HSV), Varicella- zoster virus (VZV), and Rubella virus [ 29 ]. Cytomegalovirus has been found to be the most common viral infection which triggers the immune system leading to GBS [ 11 , 29 , 30 , 31 ]. Following CMV, Epstein Barr virus is found to be the next common antecedent viral infection causing approximately 10% of total GBS cases [ 11 , 29 , 32 ]. GBS cases in children are mostly due to antecedent respiratory viral infections [ 33 ]. Antecedent infection with HEV, HAV, and Hepatitis B virus were also reported to cause GBS [ 34 , 35 , 36 ]. Rarely, infections with Adenovirus, Rubella were also observed as antecedent event in GBS patients [ 37 ].

Among the arboviruses, antecedent Zika virus infection has been widely studied in GBS. The 2013 Zika virus outbreak in French Polynesia was followed by an increased number of GBS cases [ 38 ]. The Zika virus epidemic that started in Brazil in 2016 and disseminated to 15 countries and territories increased the GBS global incidence rate 2.6 times [ 39 , 40 ]. Other arboviral infections including Dengue, Chikungunya, and Japanese Encephalitis have also been implicated in the pathogenesis of GBS. In a multinational case-control study conducted in Brazil, Argentina, and Malaysia during 2017–2019 to understand the association of GBS with antecedent arboviral infections, it was found that 55% (27/49) of patients had recent infections. Arboviral infections caused due to Dengue and Chikungunya virus were found in 4% of these cases [ 41 ]. Another study conducted in Mexico to predict the incidence of GBS owing to arboviral infections reported antecedent Zika and Dengue infections in GBS but intriguingly, GBS was not associated with antecedent Chikungunya infection [ 42 ]. Among studies conducted in India, one done in the northern region reported 11.5% (3/26) antecedent Dengue infection in GBS [ 43 ]. In another study conducted in southern India, it was found that 79.3% of GBS patients studied had antecedent infections, of which viral infections with Chikungunya virus, Japanese Encephalitis virus, and Dengue virus were prominent [ 44 ].

While the occurrence of GBS following Chikungunya infection is uncommon, it is recognised as a potential trigger for GBS, particularly during outbreaks and in regions where the virus is endemic. During the Chikungunya outbreak at Reunion Island, France in 2005–2006, Lebrun et al. reported 2 cases of GBS with antecedent Chikungunya infection. In both the patients, Chikungunya infection was confirmed by the presence anti-Chikungunya IgM and IgG antibodies in serum and CSF [ 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ]. Antecedent Chikungunya infections in GBS reported globally in the last two decades are depicted in ( Table  1 ) .

Pathogenesis of GBS

Th pathophysiology of GBS has been the subject of numerous studies, and research is still ongoing. The most accepted mechanism of pathogenesis is “molecular mimicry” at the B-cell level, particularly in the axonal variant ( Fig.  1 ) . Previous studies found a structural similarity between lipopolysaccharide on the cell membrane of C. jejuni and the glycan molecule in the ganglioside, and the antibody produced against the bacteria led to nerve cell damage through cross-reactive immunological responses [ 54 , 55 , 56 ]. Supporting this, the animal studies carried out in “acute motor axonal neuropathy rabbit model” observed molecular mimicry in acute motor axonal neuropathy (AMAN) type of GBS [ 57 ]. Anti-ganglioside antibodies have been recorded in 36% of GBS patients [ 58 ]. These antibodies have been shown to have different peripheral nerve targets. Anti-GD1a antibodies bind to paranodal myelin, nodes of Ranvier, and neuromuscular junction. Anti-GM1 and anti-GQ1B antibodies bind to a peripheral nerve or neuromuscular junction [ 59 ]. This anti-ganglioside antibody mediated disease progression through complement cascade activation and formation of membrane attack complex plays a major role in the degeneration of nerve components [ 60 ].

AIDP- “Acute Inflammatory Demyelinating Polyneuropathy,” AMAN- “Acute Motor Axonal Neuropathy,” AMSAN- “Acute Motor and Sensory Axonal Neuropathy,” MFS- “Miller Fisher Syndrome,” TNF- “Tumor Necrosis Factor,” IL- “Interleukin”.

There are a few studies done in arboviral infections that have demonstrated anti-ganglioside antibodies. Dutta et al. observed an increase in anti-GD1a, GD1b, GT1b, and GQ1b antibodies in GBS patients with antecedent Japanese Encephalitis infection [ 61 ]. In a study conducted in immunocompetent mice, an increase in anti-GD1a and GD1b antibodies was observed in Zika virus associated GBS [ 62 ]. In another study involving GBS patients with antecedent Zika virus infection, antibody against GD3 ganglioside was found to be in high [ 63 ]. In GBS patients who had a prior COVID-19 infection, antibodies against GM1, GM2, GD1a, and GQ1b have been identified [ 64 , 65 , 66 ]. In the AIDP variant, autoantibodies against cell adhesion proteins like neurofascin, NRCAM, and contactin-2 localized at Ranvier’s nodes have been suggested as possible targets [ 67 ]. Similar evidence is not well documented for Chikungunya infection. Anti-ganglioside screening has been sparsely done in GBS cases associated with antecedent Chikungunya infection. Although molecular mimicry is speculated to be the most likely mechanism for such cases, there is a lack of evidence that demonstrates viral structure mimicking neural structures. There are two pathways of pathogenesis of Neuro-Chikungunya proposed. One is the direct viral CNS infection which may explain the quick onset of neurological symptoms in GBS patients with antecedent Chikungunya infection (as short as 2 or 3 days) and the second is the PNS affection by autoimmune mechanisms. However, there is a need to generate more evidence on it as well as on the possibility of viral mutations leading to neurological complications [ 68 , 69 ].

Apart from anti-ganglioside antibodies, the epineurium and endoneurium of the nerves have demonstrated infiltration of T lymphocytes in GBS. CD4 + and CD8 + T lymphocytes, as well as macrophages, are observed in greater numbers. It is suggested that the activated T lymphocytes in infections release proinflammatory cytokines, that further activate the complement system leading to demyelination and axonal degeneration. TNF-α produced by the infiltrating T cells has a direct myelinotoxic effect on myelinated fibers, causing demyelination [ 70 ]. The exact mechanisms of pathogenesis, however, still remains unclear.

Clinical manifestations and diagnosis

GBS is caused by the autoimmune attack of peripheral nerves. After the onset of symptoms, it may take 24 hours to four weeks to reach the nadir. The clinical symptoms involved in GBS include weakness and tingling sensation of upper and/or lower limbs which may progress to paralysis of leg, arm, or facial muscles if left untreated [ 12 ].. Some patients may suffer from facial nerve palsy, oculomotor weakness, or oropharyngeal weakness. 10 to 30% GBS patients suffer from severe respiratory muscle weakness within 2 to 4 weeks and require mechanical ventilation [ 71 ]. Keesen et al. observed that in well-characterised GBS patients, respiratory involvement was more distinctively associated with antecedent Chikungunya infection as compared to other arboviral etiology [ 72 ]. Autonomic manifestations like ileus, urinary retention, fever, tachycardia or bradycardia, hypertension or hypotension are also reported in the GBS patients [ 73 , 74 , 75 ].. Fulminant GBS cases reported are characterized by the “absence of brainstem reflexes, complete tetraplegia, and respiratory arrest” [ 76 ]. Rarely, papilledema, facial myokymia, hearing loss, meningeal signs, change in mental status, vocal cord paralysis are also seen in GBS patients [ 77 ]. (Fig.  2 ) shows the clinical features seen in the different variants of GBS.

GBS variant and Clinical manifestation

National Institute of Neurological Disorders and Stroke (NINDS) GBS diagnostic criteria

AIDP- “Acute Inflammatory Demyelinating Polyneuropathy,” AMAN- “Acute Motor Axonal Neuropathy,” AMSAN- “Acute Motor and Sensory Axonal Neuropathy,” MFS- “Miller Fisher Syndrome”.

A diagnosis of GBS is mostly based on the clinical history and physical examination. “National Institute of Neurological Disorders and Stroke (NINDS)” has published the GBS diagnostic criteria that is being widely followed (Fig. 3 ) [ 78 ]. The CSF examination and electrophysiological studies provide additional details about the condition. Routine laboratory investigations such as complete blood count, tests for blood glucose, electrolyte estimation, kidney and liver function tests are done in order to exclude other underlying pathologies. Anti-ganglioside antibodies found in the serum aid in identifying the GBS variant. In GBS, CSF protein level is elevated with a normal cell count. CSF examination is also done to find albumin-cytological dissociation [ 78 ]. The severity of the symptoms can be assessed by nerve conduction studies (NCS) and electromyography, which can aid in distinguishing between the axonal and demyelinating forms. Radiological studies can aid in cases where CSF and nerve conduction studies are inconclusive. Spine Magnetic Resonance Imaging (MRI) can exclude other conditions like compressive polyradiculopathy and transverse myelitis [ 79 ].

Treatment and prognosis

Primarily IVIg (0.4 g/kg for 5 days) and plasma exchange (200–250 ml plasma/kg body weight in five sessions) are the recommended treatments for GBS which are quite effective. Due to better availability and ease of administration, IVIg is preferred over plasma exchange. Despite therapy, there is a significant mortality of 3–10% [ 78 , 80 ].

ICU admission is warranted in about 22% of the patients with GBS due to increasing respiratory insufficiency, as was the case here; severe dysfunction in swallowing, cardiac abnormalities and in rapid progression of weakness. Respiratory distress requiring mechanical ventilation has been reported in cases with antecedent Chikungunya infection. In such cases, both acute and long-term mortality are low [ 78 , 81 ].

Antiviral treatment can be considered in patients with GBS who have an ongoing treatable viral infection; however, preceding infections have usually resolved before the onset of weakness [ 78 ]. Arboviral infections including Chikungunya infection is managed by supportive measures. A few novel antiviral compounds and monoclonal antibodies are being evaluated against Chikungunya virus [ 82 , 83 , 84 ]..

Severe disability is seen in 20% of cases which require neurorehabilitation. Some of the delayed complications of GBS include neuropathic pain, postural hypotension, and fatigue. These may persist for months together [ 80 ].

In conclusion, although GBS is considered as a rare disease, there is a perceptible increase in the incidence, especially during outbreaks and pandemics of infectious disease. Many studies mentioned in the literature review have concurred the same. Here we have reported a case of GBS associated with antecedent Chikungunya infection. Chikungunya infection most often causes a self-limiting disease; however, severe complications have been reported occasionally. The case described in this paper adds to the few cases of Chikungunya infection preceding GBS reported globally. This will help physiciansunderstand the clinical course and managesuch cases better. As per the evidence in literature, it is worth noting that acute Arboviral infections including Chikungunya infection lead to GBS in a short period of time that usually ranges from a few days to a few weeks. Most of these cases require ICU support due to frequently associated respiratory insufficiency. Documentation of such cases can help public health policy makers to undertake more surveillance programs and implement appropriate control measures to reduce the burden of Arboviral infections. Along with it, an understanding of the pathogenesis may lead to the development of more directed preventive and therapeutic interventions.

Data availability

Not applicable.

Abbreviations

Guillain Barré Syndrome

Acute Inflammatory Demyelinating Polyneuropathy

Acute Motor Axonal Neuropathy

Acute Motor and Sensory Axonal Neuropathy

Miller Fisher Syndrome

Pharyngeal Cervical Brachial

Bickerstaff’s brainstem encephalitis

Intravenous Immunoglobulin

Lower Motor Neuron

Magnetic Resonance Imaging

Endotracheal tube

Electroencephalogram

Polymerase Chain Reaction

Antigen-presenting cells

Cytomegalovirus

Epstein Barr virus

Cluster of differentiation

Real-time reverse transcriptase polymerase chain reaction

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Acknowledgements

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V Sreelakshmi and Amrita Pattanaik contributed equally to this work and share first authorship.

Authors and Affiliations

Manipal Institute of Virology, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India

Sreelakshmi V., Amrita Pattanaik, Srilatha Marate & Chiranjay Mukhopadhyay

Department of Neurovirology, National Institute of Mental Health and Neurosciences (NIMHANS), Karnataka, Bengaluru, India

Reeta S Mani

Department of Neurology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India

Aparna R. Pai

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SV prepared the first draft of the manuscript and performed the virological laboratory investigations. AP was involved in conceptualisation, literature research, and manuscript editing and review. SM was responsible for literature search and manuscript editing. ARP was responsible for patient recruitment, interpretation of clinical data, manuscript editing and review. RSM and CM were responsible for critically revising the paper for important intellectual content and overall supervision. All authors have read and approved the final manuscript.

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Correspondence to Amrita Pattanaik or Aparna R. Pai .

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The additional virological investigations done were a part of the study titled, ‘Screening for antecedent viral infections in Guillain Barre Syndrome’ that was approved by the Institutional Ethical Committee (IEC), Kasturba Medical College, and Kasturba Hospital (Approval ID: 167/2022).

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Written informed consent was obtained from the patient for the publication of this report.

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The authors declare that they have no competing interests.

Authors’ information

Manipal Institute of Virology, Manipal Academy of Higher Education, Manipal, Karnataka, India.

Sreelakshmi V, Amrita Pattanaik, Srilatha Marate, Chiranjay Mukhopadhyay.

Department of Neurovirology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka, India.

Reeta S Mani.

Department of Neurology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India.

Aparna R Pai.

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V., S., Pattanaik, A., Marate, S. et al. Guillain-barré syndrome (GBS) with antecedent chikungunya infection: a case report and literature review. Neurol. Res. Pract. 6 , 21 (2024). https://doi.org/10.1186/s42466-024-00315-6

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Received : 02 December 2023

Accepted : 04 March 2024

Published : 11 April 2024

DOI : https://doi.org/10.1186/s42466-024-00315-6

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• Guillain-Barré Syndrome
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• Arboviral infections
• Chikungunya
• Molecular mimicry
• Intravenous immunoglobulin

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