Mild Form of Guillain Barre Syndrome, Clinical Characteristics and Outcome with or Without Plasmapheresis: A Local Experience

Background: Guillain-Barre syndrome is an immune mediated poly-radiculo-neuropathy with a variable clinical presentation and prognosis. Plasma exchange and Intravenous immunoglobulin are treatment options with proven efficacy by various clinical trials. But these trials demonstrate improvement in a classical and moderate to severe GBS. In clinical setting, problem may occur in treatment of those patients who present with mild symptoms & signs, clinical variants of GBS, or when the duration of weakness is > 2 weeks from onset of symptoms. Objective: To determine the frequency of mild GBS, its clinical characteristics & to compare clinical outcome of patients treated with or without plasmapheresis. Methods: Prospective, Quasi experimental study was done in Neurology, MHL from June, 2020 to June, 2022. Diagnosis of mild GBS was made on basis of patient ability to walk without support/ GBS disability score is ≤ 2. Outcome in these patients was assessed by using MRC sum score at presentation one and 3month post treatment. Results: Patients with diagnosis of GBS (n=154) were admitted and treated during 2years.out of these patients, 22(14.28%) were diagnosed as mild GBS, 18 males and 4 females. MRC Sum score at presentation 18.5, at 1-month 19.7 and at 3 month it was 19.5 on average. MRC sum score improvement noted in patients treated with plasma-pheresis at one and three months with p value less than 0.01. There was no difference in recovery with increased number of sessions of plasma-pheresis 3 versus 5 sessions at one month and 3months with p value 0.18 &0.32 respectively. Conclusion: Mild GBS is not uncommon, remained under-reported in clinical scenario. Plasma-pheresis seems to have a beneficial role in mild form of GBS


Introduction
G uillain-Barre syndrome (GBS) is an immune media- ted acute polyneuropathy with a characteristic ascending pattern of weakness with variable disease 1 pattern and prognosis.It is a worldwide disease prevalence with an annual global incidence of approxi-3(able to walk with help), 4(bedbound), 5(need ventilator 3 support) and 6 (dead).
Various treatment options are available with proven efficacy in various randomized control trials.These pharmacological treatment options are intravenous immunoglobulin (IVIG) and plasma exchange (PE).Some trials have been done on injectable steroid as first line treatment but no significant outcome making this option controversial.Both IVIG and PE are equally effective in reducing time for recovery in moderate to Treatment of mild GBS with plasma-pheresis showed duration of disease was significantly lesson with plasma 7 exchange as compared with supportive therapy along.
It is difficult to predict which mild GBS patient condition will remains stable during early clinical course of disease during observation.Treatment dilemma remained about mild form of GBS (those patients who remained stable for >2weaks or walk independently since the disease onset).Criteria for categorized GBS as mild, moderate and severe based on motor scale but did not address other symptoms like facial weakness, paresthesias which need to be addressed.There is spare or little literature/ evidence base guidelines are available regarding treatment of mild GBS.So, aim of my study is to know the frequency, clinical characteristics of mild GBS and outcome with or without treatment.

Methods
After taking approval from ethical committee of king Edward Medical University Lahore, A Prospective, Quasi experimental study was conducted in Neurology department Mayo hospital, Lahore.Medical record of total no. of GBS patients admitted in neurology department in last 2 years from June, 2020 to June 2022 was noted on predesigned proforma.Diagnosis of GBS was based on history of weakness of limbs with or without sensory disturbance, cranial nerve involvement and electrophysiological findings suggestive of GBS.Diagnosis of mild GBS was made on basis of patient ability to walk without support during their illness or GBS disability score is ≤2.All those patients who had moderate to severe GBS or a GBS disability scale of 3-6 was exclude from study.Data regarding mild GBS patients (n=8) who received plasma-pheresis (via non probability-purposive sampling technique) and patients (n=14) that did not get any definite treatment/supportive treatment only was noted.Then patients were called for follow-up in OPD and clinical assessment for outcome was done prospectively for GBS patient according to Medical Research Council (MRC)-sum score11.Outcome in both patients' groups was assessed.
Data was entered and analyzed by SPSS 23.Quantitative variables such as age, time to onset from presentation and MRC sum score, CSF findings were considered as mean and confidence interval.Qualitative variables such as gender, preceding history of fever, clinical features (signs and symptoms), plasma-pheresis and electrophysiological findings were considered frequency and percentage.Medical counsel research sum score at the time of presentation, after one and 3month were noted.Both groups were compared for outcome by using independent sample t test and p-value ≤0.05 was considered as statistically significant.
Our study showed no difference in recovery with increased number of sessions of plasma-pheresis 3 versus 5 sessions at one month and 3months with p value 0.18 &0.32 respectively.3 sessions were enough to show a statistically significant recovery.

Discussion
This was a 2-year study, being conducted between 2020 to 2022 in which, our experience 14.1% were milder form of GBS out of the total cases of 154, which

Table 3: Outcome of mild GBS patients with and without plasmapheresis
There was significant male proportion of mildly affecting patients reaching 82 percent which is higher than most studies which generally show a percentage rea-8 ching 60 percent of male pre pondence.Possible cause might be cultural as female health care is generally ignored.
Our study reported similarities regarding its prevalence in younger age group which report mostly patients 13 affected to be less than 50.
A Preceding infection 45.5 % in slightly lower than 9,13 report in 2 studies in Netherlands, which report a 72% and 58% percent respectively but is similar to a study 14 conducted in Israel.
In our study pain preceding to weakness is reported in 63.6 which is higher than reported in one study of 38 15 percent.Cranial nerve involved is 27.2 percent which 13 is lower to reported in 41%.
During electrophysiological testing there was no particular pattern observed except that the commonest finding was abnormal f waves which was reported in 91% cases and least reported finding was reduced compound motor action potential in lower limbs which was found in only in 9.1%.During NCS studying 9% had normal 16 NCS.Which is similar to the reported 6 -8%.
The average no of day to maximum weakness was around 5, which is less than reported in different studies.7 days were reported by Van Koningsveld and 8 days
There was significant difference with the CSF protein as in this study average was 92mg/dl which in contrast to the reported 3 out of 10 patients with elevated CSF elevated protein.The obvious reason seems to be the early testing of CSF protein in the above study as CSF levels are highly dependent on the e timing of testing There are limited studies available, showing response of immunotherapy to mild affected GBS patients and even less studies are done in Asia pacific region.Our study demonstrated a beneficial response of plasmapheresis in terms of early motor recovery of mild GBS patients which Is similar to the study of 108 patients with mild disease in 3 countries Serbia, Republic of Srpska -Bosnia and Herzegovina, Montenegro in a seven-year period which showed ≥1 on GBS Disability Scale after mean period of one month from disease 21 onset 83% of with plasmapheresis.
In another study, patients suffering from mild GBS who were treated with 5-day course of IVIG regained full muscle strength after 4 weeks (70% vs, 48%, p= 0.04) and the time to regain full muscle strength was shorter in the IVIG treated patients than in the untreated patients but failed to improve functional outcome after 2 weeks and also showed that 40% had residual symptoms even after 1 year.In our study there was complete recovery of muscle strength with plasmapheresis.We did 11 not use IVIG as treatment option due to cost issue.
Our study showed no difference in recovery with increased number of sessions of plasmapheresis.3 sessions were enough to show a statistically significant recovery.Another study done by the French cooperative group also showed that two PE sessions significantly shortened the time to onset of motor recovery (4 days) than supportive care (8 days) and shortened the time to hospital 7 discharge (13 vs. 18 days).
Currently the International GBS Outcome Study, a multicenter prospective cohort study on GBS is an ongoing trail investigating treatment in patients with 22 mild GBS and is expected to publish its results in 2024.
There are a few limitations of our study as sample size is small and there is no comparison available with IVIG.This is due to high cost of this treatment option.

Conclusion
Clinical characteristics for mild GBS are similar to those moderate to severe cases.Patients with mild disease may advise use of treatment like plasmapheresis to hasten early recovery.However, larger prospective randomized control trials are needed to be conducted in future.

Ethical Approval:
The Institutional Review Board, KEMU approved the study vide letter No. 1053/ RC/ KEMU.

4 severe
GBS cases, hence improved clinical outcome.Mild form of GBS, defined as a person who can walk independently but cannot run, has been under reported 5 with different studies showing different prevalence.A study conducted by Verboon.C, et al. compared treatment of mild GBS with IVIG verses supportive care only showed there is limited to no benefit to treat mild 6 GBS with IVIG in long-term outcome.

9
is same as reported by P.A. Van Doorn et al.It also comes close to the number reported by winter et al. at 12 12%.But varies with the reported number in Netherlands mild forms of Guillain-Barre´ syndrome in an 13 epidemiologic survey in the Netherlands of 28% and 8 35% reported in a population-based study in Denmark.January -March 2024 | Volume 30 | Issue 01 | Page 66

17 , 18 for
CSF.Most studies have demonstrated beneficial response to immunotherapy in severely affected pa- March 2024 | Volume 30 | Issue 01 | Page 65 reduced motor amplitude Lower Limb, 45.5% with delayed motor latency Upper Limb, 63.6% with delayed motor latency Lower Limb, all cases with normal sensory amplitude Upper and Lower Limb, 27.3% were delayed sensory latency Upper Limb same on Sensory latency Lower Limb.

Table 1 :
Descriptive parameters of GBS Patients (Sex, Preceding Viral, Symptoms, Pain and Cranial Neuropathy)

Table 2 :
Weakness (MRC Sum score) at the time of presentation, laboratory parameters and on follow up