|Year : 2019 | Volume
| Issue : 2 | Page : 88-93
Rehabilitation outcomes in patients with guillain–barré syndrome caused by zika virus
Coral Candelario-Velazquez1, Raúl Rosario-Concepcion2, Néstor Diaz3, Myriam Crespo1
1 Department of Physical and Rehabilitation Medicine, School of Medicine, University of Puerto Rico, San Juan, Puerto Rico
2 Department of Family Medicine and Sports Medicine, Mayo Clinic, Florida, USA
3 Department of Physical Medicine and Rehabilitation, Encompass Health, San Juan, Puerto Rico
|Date of Submission||29-Jan-2019|
|Date of Acceptance||02-Mar-2019|
|Date of Web Publication||29-Aug-2019|
Prof. Myriam Crespo
Department of Physical Medicine and Rehabilitation, University of Puerto Rico School of Medicine, San Juan, Puerto Rico
Source of Support: None, Conflict of Interest: None
Introduction: Zika virus (ZIKV) is transmitted by the bite of the Aedes species mosquito. Infected patients may present flu-like symptoms or even neurological deficits. In Puerto Rico (PR), an increased number of cases of ZIKV were noted in 2016 and a surveillance system was established for monitoring. As of August 2018, a total of 36,097 symptomatic cases of ZIKV had been reported in PR by the Centers for Disease Control and Prevention of the United States. One of the neurological complications secondary to ZIKV was Guillain–Barré syndrome (GBS). The surveillance system reported that 66% of patients with GBS who were tested were positive for ZIKV. This study aims to identify the functional outcomes of GBS patients related to ZIKV as compared to patients with GBS nonrelated to ZIKV during inpatient rehabilitation using functional independence measure (FIM) score. Materials and Methods: A retrospective case–control study design was used. Patients with a diagnosis of GBS admitted to an inpatient rehabilitation unit between January 1, 2016, and August 15, 2017, were deemed eligible. Patients were divided in two groups: (1) GBS-positive ZIKV (experimental) group and (2) GBS-negative ZIKV (control) group. A total of 21 patients were identified; 16 qualified for the study. The primary outcome was the admission and discharge FIM score. Results: A total of 11 (69%) patients were ZIKV positive or presumptive positive and 5 (31%) were ZIKV negative. One hundred (100%) of the patients had significantly improved FIM scores upon discharge. No significant differences between the ZIKV groups were noted on admission or discharge FIM scores. Conclusion: This study demonstrated that all GBS patients benefit from inpatient rehabilitation facility admission and therapy regardless of ZIKV status. Rehabilitation outcome is not determined by ZIKV status.
Keywords: Acute inflammatory demyelinating polyneuropathy, functional independence measure, inpatient rehabilitation facility, neurological disease
|How to cite this article:|
Candelario-Velazquez C, Rosario-Concepcion R, Diaz N, Crespo M. Rehabilitation outcomes in patients with guillain–barré syndrome caused by zika virus. J Int Soc Phys Rehabil Med 2019;2:88-93
|How to cite this URL:|
Candelario-Velazquez C, Rosario-Concepcion R, Diaz N, Crespo M. Rehabilitation outcomes in patients with guillain–barré syndrome caused by zika virus. J Int Soc Phys Rehabil Med [serial online] 2019 [cited 2019 Oct 20];2:88-93. Available from: http://www.jisprm.org/text.asp?2019/2/2/88/264756
| Introduction|| |
Zika virus (ZIKV) is mainly transmitted by the bite of an infected Aedes species mosquito. Symptoms of the disease include fever, headache, rash, joint pain, muscle pain, and conjunctivitis. Infected patients usually develop mild symptoms or may be asymptomatic. Due to an increase in the number of cases of ZIKV in different parts of the world, the Centers for Disease Control and Prevention (CDC) of the United States established a surveillance system to monitor the number of cases in Puerto Rico (PR) and the Caribbean region. As of August 2018, a total of 36,097 symptomatic cases of ZIKV had been reported by the CDC in PR.
There have been several reports of neurological complications secondary to ZIKV infection such as neonatal microcephaly, encephalitis, and Guillain–Barré syndrome (GBS)., GBS is a neurological disease caused by an autoimmune response which affects the peripheral nervous system. The pathogenesis of the disease is associated with antibodies attacking the nerve's myelin sheath or axonal membrane. In 2013, before the ZIKV epidemic, there was a GBS incidence of 1.7 per 100,000 population in PR.
A GBS surveillance system has been implemented in PR due to a rise in neurological complications associated with ZIKV. This system detected 123 cases of confirmed GBS through 2016. Of these, 107 (87%) were tested for ZIKV and 71 (66.4%) of those tested were positive for ZIKV infection.
Because of significant functional deficits associated with GBS, inpatient multidisciplinary rehabilitation has been highly recommended for postacute management with the goal of restoring functional capacity and independence.,
Few data have been published regarding the benefit of inpatient rehabilitation on function in patients with GBS due to ZIKV. It is important to know if patients with ZIKV-related GBS respond to rehabilitation in the same way as those with GBS due to other causes. Thus, this study aims to identify the functional outcomes of GBS patients infected with ZIKV as compared to patients with GBS not related to ZIKV during inpatient rehabilitation. A study performed in PR during the ZIKV outbreak concluded that GBS associated with ZIKV correlated with higher morbidity, including more dysphagia, shortness of breath, use of mechanical ventilation, and admission to an intensive care unit. As a result of that study, we hypothesized that patients with GBS related to ZIKV would have a lower admission functional independence measure (FIM) score and less gains on FIM score after the inpatient rehabilitation.
| Materials and Methods|| |
Study design and subjects
A retrospective case–control study design was used. Patients with a diagnosis of GBS admitted to an inpatient rehabilitation unit between January 1, 2016, and August 15, 2017, were eligible for record review. The study was approved by the Institutional Review Board of the Medical Sciences Campus of the University of PR.
Patients were accepted into the study if they were older than 21 years and admitted into the inpatient rehabilitation facility with a diagnosis of GBS and test results for ZIKV. The diagnosis of GBS was established using a cerebrospinal fluid sample and/or an electrodiagnostic examination. If these were not available, the diagnosis was made clinically following the Brighton Collaboration Criteria.
Patients diagnosed with GBS were divided in two groups: those who tested positive for ZIKV and those who tested negative for ZIKV (control group). A total of 21 patients were identified, and based on the inclusion criteria, a total of 16 qualified for the study. Of these, 11 tested positive for ZIKV or presumptive positive by IgM in the serum.
A data extraction sheet was created and completed for each subject. The gender, age, ZIKV diagnostic test result, GBS diagnostic test, length of stay, and medical complications were recorded.
The primary outcome of the study was the admission and discharge FIM score. The FIM measures the activities of daily living such as eating, grooming, bathing, dressing, toileting, and bowel/bladder management; functionality as transfer and mobility; and comprehension. A number between 0 and 7 is assigned depending on the level of assistance needed to complete a task [Appendix]. This scale has been used previously to evaluate progress in GBS patients during inpatient rehabilitation and has been shown to be a valid and reliable tool to measure functional status and progress during rehabilitation.,, Because this was a retrospective study, the therapists conducting the FIM evaluation were blinded as to the objectives of the study at the time of the evaluations. Therapists at the institution are trained for FIM evaluation.
The secondary outcomes of the study were the length of stay in the rehabilitation hospital and the number of medical complications.
Data analysis was conducted using Statistical Package for the Social Sciences (IBM, Armonk, NY, USA) software package. Analysis of variance was conducted to compare the admission FIM and the discharge FIM. An independent sample's t-test was used to compare the admission and discharge FIM between groups.
| Results|| |
Patients and diagnosis
A total of 21 patients with confirmed diagnosis of GBS were admitted to our inpatient rehabilitation facility from January 1, 2016, to August 15, 2017; 16 in 2016 and 5 in 2017. The number of patients admitted to the inpatient rehabilitation facility with the diagnosis of GBS increased during the Zika epidemic. For example, in 2014 and 2015, GBS was the diagnosis on admission in a total of eight and five patients, respectively. Of the 21 patients in the present study, one patient was not ZIKV-tested and the results of the test in four patients were not available at the moment of the analysis; as such, they were excluded from the study. This resulted in a final study sample of 16 patients with GBS and test results for ZIKV. There were no significant differences between the two groups in mean age or gender representation [Table 1].
All the patients had clinical symptoms of GBS. A total of 11 (69%) patients were ZIKV positive or presumptive positive and 5 (31%) were ZIKV negative. The ZIKV test revealed 10 positive or presumptive positive results in the serum test and 1 positive in both cerebrospinal fluid and serum test. According to the Brighton Collaboration Criteria, GBS diagnosis results were 4 (25%), 9 (56%), and 3 (19%) for levels 1, 2, and 3, respectively [Table 2].
|Table 2: Results of zika virus tests, brighton criteria, mechanical ventilation and length of stay|
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Functional independence measure scores
The mean admission FIM was 51 points in the ZIKV-positive group and 47 points in the ZIKV-negative group. The mean discharge FIM was 88 in the ZIKV-positive group and 83 in the ZIKV-negative group. No significant differences between groups were noted on either FIM score [Figure 1]. However, both groups showed a significant increase in FIM scores with rehabilitation (P <.001).
|Figure 1: Comparison between admission and discharge FIM score. P value represents the significance between groups on admission FIM and discharge FIM. Adm: Admission; Dis: Discharge, ZIKV: Zika virus; Pos: Positive, Neg: Negative, FIM: Functional independence measure|
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Length of stay
The mean length of stay in the inpatient rehabilitation facility was 16.3 days with significant difference between groups. The ZIK-negative group had more days at the inpatient rehabilitation unit (P < 0.03) [Table 2].
The most severe complication during acute hospitalization was respiratory failure requiring mechanical ventilation in 6 (54.5%) of the ZIKV-positive patients and 1 (20%) of the ZIKV-negative patients. In addition, complications in the ZIKV-positive group during inpatient rehabilitation included urinary tract infections in four patients (36.3%), bowel problems (constipation or diarrhea) in five patients (45%), and pneumonia in one patient (0.09%). One patient from the ZIKV-positive group was transferred back to the acute care hospital due to sepsis and then readmitted to the rehabilitation facility. On the other hand, complications in the negative ZIKV group in the rehabilitation hospital included urinary tract infection in 1 (20%) patient and bowel problems in 2 (40%) patients. One patient from the ZIKV negative had respiratory failure requiring transfer back to the acute care hospital. No cardiac complications or deaths occurred [Table 2].
| Discussion|| |
The most important finding of the present study was that the FIM score gain in GBS patients is independent of the ZIKV status. To our knowledge, this is the first report of the effects of ZIKV on the functional recovery of patients with GBS.
The inpatient rehabilitation center admitted a total of 21 patients with GBS during the evaluated time frame, suggesting an increased incidence of GBS during the Zika epidemic in PR. The presence of ZIKV in our study population (69% positive and 31% negative) is consistent with that reported by the CDC in a larger sample of 106 hospitalized GBS patients in 2016 (67% positive, 34% negative). Other studies have described the association between GBS and ZIKV., One study in French Polynesia reported that cases were ZIKV IgM positive in 93% of the GBS patients. Another study in Colombia reported an association of 40%. This results in an evident association of arbovirus with increased risk of GBS.
There is evidence that inpatient multidisciplinary rehabilitation improves FIM scores, disability, and quality of life in patients with GBS., Our study shows that these outcomes are also possible in patients with ZIKV despite the reported effects of the ZIKV in the central nervous system.
Length of stay during inpatient rehabilitation can be considered as a proxy for the severity of the illness. The mean length of stay for patients with GBS has been reported to be 21 and 26 days longer than the average for both groups in the present study., In our experience, this may be secondary to issues related to health insurance in PR, where insurance companies authorize fewer days at inpatient rehabilitation facilities, regardless of diagnosis, and encourage more ambulatory therapy. The experimental group had fewer days at the rehabilitation unit. This finding may be associated with longer stay at the acute care facility and the natural history of GBS, which can result on a progressive improvement of neurological symptoms. The increased length of stay at the acute care hospital was related to an increased use of mechanical ventilation by the ZIKV-positive patients. These findings are similar to those reported previously comparing the use of mechanical ventilation in GBS related to ZIKV (31%) versus non-ZIKV GBS patients (11%). Nevertheless, our patients showed significant improvement in FIM scores and gains with 36 and 37 points in the ZIKV-positive group and ZIKV-negative group, respectively (P <0.001). Previous studies reported an average FIM gain of 33.5 points in patients with GBS patients. This emphasizes the importance of rehabilitation in GBS patients, regardless of the cause.
There are a few case reports in the medical literature of GBS in patients with a different arbovirus infection that have the same vector. For example, cases of dengue fever in Malaysia and Brazil have been associated with GBS., In those reports, all patients recovered neurological function between 9 days and 1 year postillness. In addition, GBS associated with the Chikungunya virus was reported in the French West Indies, resulting in two deaths and seven cases that achieved functional recovery. These case reports suggest that most GBS cases related to arbovirus infection can have good physical recovery, although a few patients may have significant complications, including death.
One of the limitations of the present study is the relatively small number of patients recruited. PR was one of the countries with more cases of ZIKV reported in America, but our recruitment was limited because the Guillain–Barré Passive Surveillance System was established very recently, in February 2016. To date, it is possible that some cases of GBS were not tested for ZIKV since the test was not done routinely at the beginning of the crisis. Further, not every GBS patient on the island has access to an inpatient rehabilitation facility. In addition, because this is a retrospective chart review, some information regarding complications and results of diagnostic tests may be missing from the chart limiting the number of patients that qualified for the study. Finally, the present study was limited to progression during the inpatient rehabilitation phase only and did not include long-term follow-ups after discharge.
| Conclusion|| |
This study demonstrated that ZIKV status in patients with GBS does not affect inpatient rehabilitation outcomes. Patients with GBS showed significant functional gains during their stay at an inpatient rehabilitation unit. Future investigations including the ambulatory phase of rehabilitation are needed to determine the long-term consequences of Zika infection associated with GBS.
We would like to thank Walter Frontera, MD for his editorial assistance in the preparation of the manuscript. We also would like to thank Olfa Reyes from the Epidemiology Department of Healthsouth Rehabilitation Hospital for her help in gathering CDC data on the patients included.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
da Silva IR, Frontera JA, Bispo de Filippis AM, Nascimento OJ; RIO-GBS-ZIKV Research Group. Neurologic complications associated with the Zika virus in Brazilian adults. JAMA Neurol 2017;74:1190-8.
Esposito S, Longo MR. Guillain-Barré syndrome. Autoimmun Rev 2017;16:96-101.
Salinas JL, Major CG, Pastula DM, Dirlikov E, Styczynski A, Luciano CA, et al.
Incidence and clinical characteristics of Guillain-Barré syndrome before the introduction of Zika virus in puerto rico. J Neurol Sci 2017;377:102-6.
Dirlikov E, Major CG, Medina NA, Lugo-Robles R, Matos D, Muñoz-Jordan JL, et al.
Clinical features of Guillain-Barré syndrome with vs. without Zika virus infection, Puerto Rico, 2016. JAMA Neurol 2018;75:1089-97.
Khan F, Ng L, Amatya B, Brand C, Turner-Stokes L. Multidisciplinary care for Guillain-Barré syndrome. Eur J Phys Rehabil Med 2011;47:607-12.
Meythaler JM, DeVivo MJ, Braswell WC. Rehabilitation outcomes of patients who have developed Guillain-Barré syndrome. Am J Phys Med Rehabil 1997;76:411-9.
Sejvar JJ, Kohl KS, Gidudu J, Amato A, Bakshi N, Baxter R, et al.
Guillain-Barré syndrome and Fisher syndrome: Case definitions and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine 2011;29:599-612.
Prasad R, Hellawell DJ, Pentland B. Usefulness of the functional independence measure (FIM), its subscales and individual items as outcome measures in Guillain Barré syndrome. Int J Rehabil Res 2001;24:59-64.
Dodds TA, Martin DP, Stolov WC, Deyo RA. A validation of the functional independence measurement and its performance among rehabilitation inpatients. Arch Phys Med Rehabil 1993;74:531-6.
Cao-Lormeau VM, Blake A, Mons S, Lastere S, Roche C, Vanhomwegen J, et al.
Guillain-Barré syndrome outbreak associated with Zika virus infection in French Polynesia: A case-control study. Lancet 2016;387:1531-9.
Parra B, Lizarazo J, Jiménez-Arango JA, Zea-Vera AF, González-Manrique G, Vargas J, et al.
Guillain-Barré syndrome associated with Zika virus infection in Colombia. N Engl J Med 2016;375:1513-23.
Khan F, Amatya B. Rehabilitation interventions in patients with acute demyelinating inflammatory polyneuropathy: A systematic review. Eur J Phys Rehabil Med 2012;48:507-22.
Andrews AW, Middleton A. Improvement during inpatient rehabilitation among older adults with Guillain-Barré syndrome, multiple sclerosis, Parkinson disease, and stroke. Am J Phys Med Rehabil 2018;97:879-84.
Boo YL, Aris MA, Chin PW, Sulaiman WA, Basri H, Hoo FK. Guillain-Barré syndrome complicating dengue fever: Two case reports. Ci Ji Yi Xue Za Zhi 2016;28:157-9.
Fragoso YD, Gomes S, Brooks JB, Matta AP, Ruocco HH, Tauil CB, et al.
Guillain-Barré syndrome and dengue fever: Report on ten new cases in Brazil. Arq Neuropsiquiatr 2016;74:1039-40.
Balavoine S, Pircher M, Hoen B, Herrmann-Storck C, Najioullah F, Madeux B, et al.
Guillain-Barré syndrome and chikungunya: Description of all cases diagnosed during the 2014 outbreak in the French West Indies. Am J Trop Med Hyg 2017;97:356-60.
[Table 1], [Table 2]