|Ahead of print
|Clinical spectrum and outcome of guillain-barré syndrome with plasmapheresis
Safia Bano1, Zomer Sardar2, Muhammad Ahmar3, Sumayyah Liaquat4, Bilal Shafiq5, Ahsan Numan1
1 Department of Neurology, King Edward Medical University, Lahore, Pakistan
2 Department of Neurology, District Hospital Nankana Sahib Lahore, Pakistan
3 Department of Neurology, Social Security Hospital, Lahore, Pakistan
4 Department of Neurology, Hussain Lakhani Hospital, Karachi, Pakistan
5 Department of Neurology, Mayo Hospital, King Edward Medical University, Lahore, Pakistan
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|Date of Submission||21-Apr-2022|
|Date of Decision||16-May-2022|
|Date of Acceptance||16-May-2022|
|Date of Web Publication||20-Oct-2022|
Context: Guillain-Barré syndrome (GBS) is an acute inflammatory neuropathy and has several electrophysiological subtypes and clinical variants. Treatment is mainly supportive and immunotherapy is given to shorten the disease course. Aims: The aim of this study was to define the outcome of GBS with plasmapheresis and to determine its clinical spectrum. Materials and Methods: The prospective study was done at Mayo Hospital, Lahore, for 1 year from November 2020 to November 2021. The diagnosis of GBS was made on Brighton criteria for GBS. The outcome of therapy was assessed at 3 and 6 months, using the Medical Research Council Scale and Hughes Functional Grading Scale (HFGS). Results: A total of 50 patients were enrolled in the study. Twenty-seven (54%) were males and 23 (46%) were females. Seventeen (34%) had acute motor axonal neuropathy, 16 (32%) had acute motor and sensory axonal neuropathy, 15 (30%) had acute inflammatory demyelinating polyradiculoneuropathy, and 2 (4%) had Miller-Fisher syndrome. Plasmapheresis was done in all patients. HFGS score was assessed at discharge, at 3 months, and after 6 months of illness onset. The improvement in mean HFGS score was 2.79 ± 0.41 at 3 months and 1.94 ± 0.25 at 6 months of symptoms onset from the mean score of 3.46 ± 0.93 at the time of discharge from the hospital. Conclusion: Excellent outcome was observed after plasmapheresis. Majority of participants were able to walk without support at the 6-month follow-up. Plasmapheresis should be initiated early in the management of GBS where intravenous immunoglobulins are costly.
Keywords: Guillain-Barré syndrome, Hughes Functional Grading Scale, intravenous immunoglobulins, outcome, plasmapheresis
|How to cite this URL:|
Bano S, Sardar Z, Ahmar M, Liaquat S, Shafiq B, Numan A. Clinical spectrum and outcome of guillain-barré syndrome with plasmapheresis. Indian J Med Spec [Epub ahead of print] [cited 2022 Dec 5]. Available from: http://www.ijms.in/preprintarticle.asp?id=359148
| Introduction|| |
Guillain-Barré syndrome (GBS) is an acute peripheral demyelinating disease that affects multiple nerves and nerve roots. Management is mainly supportive and treatment with immunotherapy (intravenous immunoglobulin [IVIG] or plasmapheresis) is used to shorten the disease course. Cochrane review published in 2017 summarized that the treatment with plasmapheresis reduced time on the ventilator, time to walk without assistance, and time to recovery of full muscle strength.
The primary aim of this study was to define the outcome of plasmapheresis as a first-line treatment where IVIG is not cost-effective. Our secondary objective was to delineate the various clinical presentations and electrophysiological subtypes of GBS.
| Materials and Methods|| |
A prospective, single-center, observational, cross-sectional study was conducted in the Department of Neurology, Mayo Hospital Lahore, Pakistan. The study was approved by the ethical and institutional review board of King Edward Medical University.
Diagnosed GBS patients who fulfilled Brighton criteria for GBS, with the age ranged between 13-70 years, both genders, and who fulfilled the criteria for plasmapheresis were included in the study. If any of the following were present, the patient was considered for plasmapheresis:
- Who had progressive weakness
- Who could not walk independently
- Needed help in the activity of daily life
- MRC <4 in limbs.
Those patients who could walk independently with the nonprogressive disease, patients who had acute flaccid paralysis due to other causes, and those in whom plasmapheresis was contraindicated were excluded from the study. Informed and written consent was obtained.
Autonomic dysfunction was labeled if one of the following was present: resting tachycardia (heart rate >100 bpm), bradycardia (heart rate <60 bpm), paroxysmal hypertension, postural hypotension (20/10 mmHg drop in systolic/diastolic pressure), arrhythmia, and urinary retention. Invasive mechanical ventilation was provided if a patient had any of the following: respiratory rate more than 30/min, chest expansion <2 cm, single-breath counts <20, arterial partial pressure of carbon dioxide (PaCO2) >50 mmHg with an arterial pH <7.25, and arterial partial pressure of oxygen (PaO2) with a supplemental fraction of inspired oxygen FiO2 of <55 mmHg.
Detailed history, time lapsed before presentation to hospital, history of fever, clinical symptoms and signs, and vital signs were noted on predesigned proforma. Disability and outcome were measured using Hughes Functional Grading Scale (HFGS) and grading of motor power was done by the Medical Research Council (MRC) Scale for muscle strength. MRC scale is a widely used method to assess limb power of key muscle groups against examiner resistance and it ranges from Grade 5 (normal power) to Grade 0 (no visible contraction). Grade 1 indicates flicker of contraction; Grade 2 denotes active movement with gravity eliminated; in Grade 3, movement is possible against gravity but not against resistance; and Grade 4 is labeled when the active movement against resistance is possible.
All patients were admitted to the intensive care unit as per the protocol of the department. Plasmapheresis (200–250 ml/kg, 0.9% normal saline was used as replacement fluid) was initiated within 48 hours of admission. A total of five sessions were done in all patients on alternate days in approximately 10 days. Muscle strength was checked at discharge and was followed up in the neurology clinic at 3 months and then at 6 months. The neurological examination was performed by Neurologists on follow-up who were not involved in the study to avoid bias.
Data were analyzed using the SPSS version 22 (IBM SPSS Statistics version 22). Quantitative variables such as age, time to onset from presentation, HFGS score, and MRC grade were considered as mean and standard deviation. Qualitative variables such as gender, preceding history of fever, clinical features (signs and symptoms), and electrophysiological subtypes were considered frequency and percentage. Poststratification of data was done using Chi-square according to the disability outcome (HFGS score) at 3 and 6 months with age groups, gender, and duration of illness. P < 0.05 was considered significant.
| Results|| |
The study included a total of 50 patients. Males (n = 27, 54%) were noted to be more affected than females (n = 23, 46%). The mean age of the sample was 30.74 ± 12.4 years. The majority of patients (n = 29, 58%) were between 21 and 40 years of age. A large number of (n = 33, 66%) patients belonged to middle socioeconomic background [Table 1].
History of preceding illness (fever) was present in 22 (44%) patients. Most (n = 32, 64%) patients had less than a week duration of symptoms at presentation to the hospital. The mean duration of illness was 6.48 ± 4.09 days [Table 2].
In electrophysiological studies, of 50 patients, the most observed subtype was acute motor axonal neuropathy (AMAN) (n = 17, 34%), while the second-most frequent subtype observed was acute motor and sensory axonal neuropathy (AMSAN) (n = 16, 32%). Only 15 (30%) patients demonstrated acute inflammatory demyelinating polyradiculoneuropathy (AIDP) subtype [Figure 1].
|Figure 1: GBS electrophysiological subtypes (n = 50). AMAN: acute motor axonal neuropathy, AMSAN: acute motor and sensory axonal neuropathy, AIDP: acute inflammatory demyelinating polyradiculoneuropathy, MFS: miller-Fisher syndrome|
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With regard to clinical examination, half of the patients (50%) had a facial weakness (unilateral n = 8, 16%, bilateral in n = 17, 34%), 9 (18%) patients had bulbar involvement, and 2 (4%) patients had Miller-Fisher syndrome. During the hospital stay, 14 (28%) patients experienced one of the autonomic irregularities (hypotension, hypertension, tachycardia, bradycardia, or urinary retention). Progression in motor weakness was reported in 39 (78%) patients, and 11 (22%) required mechanical ventilation due to severe respiratory muscle weakness [Table 2].
The mean MRC score on admission was 2.67 ± 1.06, which improved to a mean MRC score of 3.6 ± 0.84 at discharge. On follow-up visits at 3 months and 6 months, considerable improvement in MRC score was observed at 4.1 ± 0.63 and 4.78 ± 0.52, respectively [Figure 2].
|Figure 2: The mean MRC grade on admission, at discharge, and at 3 and 6-month follow-up. MRC: Medical Research Council|
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HFGS score improved, with a mean of 2.79 ± 0.41 at 3 months and 1.94 ± 0.25 at 6 months. At the time of discharge, 26 (52%) had a disability score of four (bedbound). At 3 months, 38 (76%) participants could walk 5 meters with help. At 6 months, 90% (n = 45) of the patients were able to walk without support (HFGS score 2) [Table 3].
On average, 94% (n = 47) noted significant improvement in muscle strength after plasmapheresis. Two (4%) patients expired during the intensive care unit stay complicated by sepsis. One (2%) patient left against medical advice.
Poststratification of disability outcome at 3 and 6 months (HFGS score) with age groups (P = 0.228), gender (P = 0.654), and duration of illness at presentation (P = 0.278) demonstrated no significant association [Table 4].
| Discussion|| |
GBS incidence is 0.4/100,000 per year. Treatment of GBS is often challenging as it is associated with significant disability. IVIG is recommended first-line treatment. Both IVIG and plasmapheresis are effective immunomodulatory therapies in the treatment of GBS. Males were disproportionately higher in our study, and previous research from other countries has found a similar pattern. Similar findings were reported by Javed et al. in 2013. A study from Saudi Arabia by Alanazy et al. reported a preponderance of males, whose ages ranged between 26.25 and 53.5 years. The results of our study are in concordance with these studies.
Bacterial infections (Campylobacter jejuni, Mycoplasma pneumoniae, and Haemophilus Influenzae) and viral infections (Epstein-Barr virus, influenza virus, herpes simplex virus, West Nile virus, Zika virus, and HIV) are reported as antecedent infections in GBS. Respiratory infections are the most commonly observed infection in GBS., In Hao et al.'s study, prior history of infection was reported in 17% (H. influenzae) of patients. In Ramos et al.'s study, 65% of patients had C. jejuni infection. A history of preceding fever was declared by 22 (44%) of participants in this study.
Electrophysiological diagnosis differs according to region. AMAN is the most common subtype found in Central and South America, as well as Japan and China. The axonal pattern is also seen in the Israeli population. Demyelinating patterns are more common in Europe and North America. It is unknown what causes regional disparities in subtypes. AMAN was the most common electrophysiological subtype observed in our study, accounting for 34% of GBS cases, which is consistent with reports from Central and South America, Japan, and China. The second-most prevalent electrophysiological subtype was AMSAN (32%), whereas AIDP was observed only in 30% of patients.
Two-thirds of patients with GBS have autonomic nerve involvement. Patients with concurrent autonomic dysfunction have significantly higher mortality., Autonomic dysfunction was found in 28% of our patients. In contrast, Singh et al.'s study found autonomic dysfunction in 41.53% of participants. One of the manifestations of autonomic dysfunction was observed in 38% of patients in Chakraborty et al.'s study. In comparison to the previous studies, our study revealed a lower frequency of autonomic symptoms that might be due to the small sample size. In the literature, 30% of GBS patients experience respiratory muscle weakness. In our study, 22% of patients required invasive ventilatory support. There is not much of a difference between our findings and those of other studies.,
According to reports in literature, cranial nerve involvement affects 30%–46% of GBS patients. Clinically, 50% (n = 25) of our patients had a facial weakness (unilateral or bilateral), bulbar weakness was seen in only 9 (18%), and Miller-Fischer presentation was observed in only 2 (4%) of our patients. The majority of the studies show that the facial nerve is the most affected cranial nerve in GBS, followed by bulbar involvement, which is consistent with our findings.
Plasmapheresis is shown to be more beneficial than IVIG in treating severe and axonal GBS in previous studies. According to a study by Chevret et al., patients can expect to recover completely within a year after plasmapheresis with no adverse side effects. At 3 and 6 months, our analysis revealed that muscle power (MRC grade) had improved by at least two grades. In terms of HFGS score, the majority of our patients (n = 26, 52%) were bedbound at discharge, but at 6-month follow-up, the majority (n = 45, 90%) were able to walk without a stick. In patients with acute inflammatory demyelinating neuropathy, Javed et al. reported a 90% improvement rate, which is almost identical to our findings. Plasmapheresis is also indicated in patients who are not responding to IVIG, have axonal involvement, or have a combination of these symptoms., No significant association was observed with HFGS score at 3 and 6 months after symptoms onset with age groups (P = 0.228), gender (P = 0.654), and duration of illness at presentation (P = 0.278).
The cost of IVIG is quite high compared to plasmapheresis. The cost of one cycle of IVIG is around five lac PKR (2500 USD), whereas, one session of plasmapheresis costs around 15 thousand PKR in our tertiary care setup. Plasmapheresis is cost effective and results in terms of improvement in functional status are striking in literature.
There are few limitations of this study such as the small sample size. Second, a comparison with IVIG was not done as IVIG is expensive in our setting.
| Conclusion|| |
Our study demonstrated a striking outcome of plasmapheresis in patients with GBS. Although IVIG is easy to use, they are costly as compared to plasmapheresis, latter is less costly and more readily accessible in our settings while being equally effective. As a result, in resource-constrained settings, plasmapheresis should be considered a first-line treatment. A comparative study with IVIG and a bigger sample size is needed.
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Conflicts of interest
There are no conflicts of interest.
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District Hospital Nankana Sahib Lahore
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]
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