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ORIGINAL CONTRIBUTIONS

Received: January 22^nd 2014

Accepted: July 12^th 2015

Features of Guillain-Barre syndrome in adults: results of a university hospital

Daniel de la O-Peña,^a Martín Robles-Figueroa,^a Quetzalcóatl Chávez-Peña,^a Martín Bedolla-Barajas^b

^aServicio de Medicina Interna

^bServicio de Alergia e Inmunología Clínica

Nuevo Hospital Civil de Guadalajara “Dr. Juan I. Menchaca”, Guadalajara, Jalisco, México

Communication with: Daniel de la O-Peña

Telephone: (998) 802 2930

Email: dop_80@hotmail.com

Background: Guillain-Barré syndrome (GBS) has a cosmopolitan distribution. Its course is usually mild and tends to limit itself, but in severe cases it can cause death. The aim of this article is to describe the characteristics of a group of adults with GBS diagnosed and treated at a university hospital.

Methods: All cases of GBS that occurred between January 1, 2005 to December 31, 2009 were analyzed. The clinical records were reviewed through the implementation of a structured survey that included the following sections: patient identification, clinical data, history of infection, season of occurrence, rates of electrophysiological variants, and lethality.

Results: A total of 45 patients were included; the male to female ratio was 1.4: 1 and the mean age was 48.2 ± 16.0 years. The season with the highest number of cases was the summer. History of intestinal infection was present in 40 % of patients, and respiratory infection in 24.4%. The lethality associated with GBS was 11.1 % (95 % CI, 4.4-23.9), fatal cases occurred in patients older than the survivors (65.2 ± 15.0 versus 46.0 ± 14.9, p = 0.01). The most common variant was acute motor axonal neuropathy (64.4 %); there were four cases of Miller Fisher syndrome.

Conclusions: The most common electromyographic variant of GBS was acute motor axonal neuropathy. The highest number of cases was observed during the summer season.

Keywords: Guillain-Barre syndrome, Polyneuropathiers, Autoinmune diseases of the nervous system.

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Guillain-Barré syndrome (GBS) is defined by the presence of flaccid paralysis with areflexia, accompanied by sensory disturbances and albuminocytologic dissociation in the cerebrospinal fluid (CSF); it is considered an inflammatory autoimmune polyneuropathy.¹ Its distribution is cosmopolitan and its incidence has been estimated at 1-2 cases per 100,000 inhabitants; it generally affects all age groups, but appears most in young adults and older adults.²

GBS had historically been regarded as one single disease, but it is now known to be a heterogeneous syndrome characterized by multiple variants. According to electrophysiological tests, the following categories are recognized: acute inflammatory demyelinating polyradiculoneuropathy (AIDP) known as the classic variant, as it appears in 85 to 90% of cases; other modalities are Miller Fisher syndrome (MFS), acute motor axonal neuropathy (AMAN), and acute motor and sensory axonal neuropathy (AMSAN).² A relevant fact is that the distribution of electrophysiological variants is not uniform, as it often depends on weather conditions, age, or socioeconomic status, among others.^3-6

Although the pathogenesis of GBS remains unclear, it is often preceded by an infection, either respiratory or intestinal.^7-10 On the other hand, several factors have been associated with poor prognosis in subjects suffering from GBS, including: advanced age, abrupt onset of the disease, need for mechanical ventilation, and previous history of diarrheal disease.^7,11,12 Electrophysiological tests may have prognostic value, especially when performed within five weeks of the onset of illness.⁷

GBS ​​lethality ranges from 5 to 20%, and the usual causes are: acute respiratory distress syndrome, pulmonary embolism, sepsis, or cardiovascular causes.^13-15

To our knowledge, there are no previous results of GBS characterization in western Mexico and, as the weather and socio-economic conditions in this region of the country are different, it is possible that the clinical behavior may be different. Consequently, the purpose of our study is to describe the clinical findings of a group of adults with GBS who were diagnosed and treated at a university hospital.

Methods

This research was approved by the Research and Ethics Committees of the Nuevo Hospital Civil de Guadalajara “Dr. Juan I. Menchaca”.

A descriptive and retrospective study analyzed all GBS cases that occurred between January 1, 2005 and December 31, 2009 and who received medical care in the Internal Medicine department.

To obtain the data, a structured form was applied to patient clinical records; the instrument included the following sections: patient identification, clinical data, history of infection, season of GBS occurrence, electrophysiological variant, and lethality. All electrocardiograms (ECG) recorded at patient admission were also reviewed in order to detect autonomic disorders, as were the characteristics of CSF and data related to the treatment administered.

According to electromyography findings, subjects were categorized into 4 groups: MSF, AMAN, AIDP, and AMSAN; conventionally for this study, patients were analyzed by the following age groups: 20-39 years, 40-59 years, and ≥ 60 years.

GBS diagnosis was established following the clinical criteria proposed by Asbury and Cornblath,² which consist of the presence of progressive motor weakness in more than one limb and osteo-tendinous areflexia; there are other additional criteria that support the diagnosis such as: progression of symptoms up to four weeks, relative symmetry of symptoms, mild sensitive signs or symptoms, involvement of cranial nerves (especially bilateral facial paralysis), beginning of recovery between 2 and 4 weeks after cessation of progression, autonomic dysfunction, absence of fever at disease onset, protein levels less than 10 cells/mm³, and the typical findings in neurophysiological tests. As for the variants of GBS, electromyography identifies AIDP as the one where weakness begins in the lower limbs,¹⁶ then there is oropharyngeal and facial weakness, numbness in the hands, pain typically located in the back and limbs,^17,18 respiratory failure due to muscle weakness associated with mechanically assisted ventilation, and signs of dysautonomia.^19,20 The AMAN variant differs from AIDP because it mostly involves the motor nerve part; occasionally deep osteo-tendon reflexes may be preserved.²¹ The AMSAN variant has greater severity relative to AMAN, affecting sensory and motor fibers with a marked axonal degeneration.²² Miller Fisher syndrome is typically characterized by signs of ophthalmoplegia accompanied by ataxia and areflexia.²³

Statistical analysis

The quantitative variables are presented as mean and standard deviation, or median if necessary; frequency was calculated for qualitative variables. For contrast of continuous variables, Student’s t test was used for independent groups or ANOVA. Chi-squared test or Kruskal-Wallis test was applied for the comparison of proportions. Statistical significance was set at a p-value ≤ 0.05.

The cumulative incidence of GBS was estimated by considering the number of inhabitants aged ≥ 18 years living in the state of Jalisco as the population at risk (4,513,718 inhabitants); for this investigation the Population Census data for the state of Jalisco were consulted.²⁴ For the lethality associated with GBS, frequency was calculated and its respective confidence interval was estimated at 95% (CI 95%).

Statistical analysis of the data was performed with the IBM program SPSS version 20.0 for Windows (IBM Corporation, Armonk, NY, USA).

Results

During the review period, 45 patients with GBS were identified, a median of 4 cases per year. The years with the highest and lowest numbers of cases were 2008 with 19 cases, and 2005 with 3.

The cumulative incidence was 1 case per 100,000 inhabitants. In total, there were 26 men and 19 women (42.2%), with a ratio of 1.4:1 in favor of men. Table I shows the clinical characteristics of patients according to electrophysiological variant. The mean age of the study group was 48.2 ± 16.0 years (lower limit 20 and upper limit 79), with no significant difference according to variant; the highest number of cases was observed in the decades of life from 40-50 years and 50-60 years (Figure 1). Most patients resided in the metropolitan area of ​​Guadalajara, 43/45 cases (95.6%), of which 18 (40%) corresponded to the municipality of Guadalajara; one case came from a different country. The season with the highest number of cases of GBS was the summer (Figure 2); during this season, the most frequent variants were AMAN, AMSAN, and AIDP, while during the winter it was MFS. The history of intestinal infection was 40% and respiratory infection 24.4%; the latter was significantly associated with electrophysiological variant (p = 0.029). One case was associated with the administration of a vaccine, without specifying the type, and one case was related to exposure to organophosphates. The overall median length of hospital stay was 8 days. The lethality associated with GBS was 11.1% (95% CI, 4.4-23.9). The average age of fatal cases was significantly higher than that of the cases who survived (65.2 ± 15.0 vs. 46.0 ± 14.9, p = 0.01). The largest number of deaths occurred in the group of older adults.

Table II shows the clinical manifestations of GBS according to the electrophysiological variant. Among the symptoms, weakness of all 4 limbs was found in 100% of cases with AIDP and MFS. Weakness of the facial muscles was most frequent in patients with MFS (75%), and exclusive weakness of pelvic members was most frequent in AMSAN (50%). As for signs, sensory disorders were most common in MFS (50%). Disorder of at least one cranial nerve was significantly associated with electrophysiological variant, and cranial nerves VII and X were the most affected. Of the dysautonomias, only tachycardia was related to variant. Only 28 patients had the report of lumbar puncture findings, and CSF dissociation was documented in almost 70% of cases. MFS patients showed greater need for care with mechanical ventilation. 

For electrophysiological findings according to age group, the most common variant was AMAN (64.4%); of the 45 patients, four of them corresponded to MFS, and the presence of this particular subtype tended to increase with age (Table III).

Discussion

Our study shows the following relevant findings: the similarity of GBS incidence with previous studies.^3,13,25 This behavior reveals that regardless of ethnicity, socioeconomics, or environmental characteristics, the disease is uniformly distributed in the world. Furthermore, GBS tends to be more common in men, and our results are consistent with this pattern.^3,5,6,26 Finally, the electrophysiological variant most commonly identified was AMAN. Thus, our study is first to describe the clinical behavior of GBS in a series of patients treated at a university hospital in western Mexico.

The most common electrophysiological variant was AMAN, which has been shown to almost always be preceded by an infection by Campylobacter jejuni.^8,21 Although 41.4% of our patients had this variant, it was not possible to identify this microorganism, as detection is not routinely performed, which is an interesting point to research in other studies looking to establish association.

The average age of our study group was consistent with that reported in other studies, both in Mexico and in other countries.^3,27 We observed a bimodal distribution of the disease, with a first peak from 40-50 years, and another from 50-60 years, which is similar to findings documented by Melano-Carranzo et al.,²⁶ while Arami et al. observed it during the decade from 60 to 69, and the second peak between 70 and 79 years.⁵ The aging process makes it likely that GBS is more common, and the explanation can be found in changes that occur in the immune system (changes in regulation of cytokine secretion such as IL-6 and TNF-alpha) and increased production of autoantibodies.^28,29 The fact that it is presented more frequently among the older population is relevant because one prognostic criterion in subjects with this disease is age: the older, the less optimistic the prognosis.^7,11

As for the type of region that patients came from (urban or rural), there is clear predominance of subjects from the urban area; we believe that this finding is related to the population density that exists in our metropolitan area, as well as this population’s easy access to health systems. Arami et al. have previously described this epidemiological behavior.⁵

History of infection previous to onset of GBS symptoms was documented in 60% of cases, an amount similar to the average reported in other studies.^3-6,30 However, unlike studies from Taiwan, Iran, or even Mexico, the frequency of gastrointestinal infections overtook respiratory tract infections,^4-6,30 hence perhaps the explanation why most of the cases in our study were presented in the summer. We believe that this finding is highly important because gastrointestinal infections are intimately associated with some electromyography variables, as in the case of AMAN.

In Mexico, the seasonal preference had not been previously documented; some studies found prevalence during the winter months,³¹ but this was in the pediatric population.

As for the frequency of signs and symptoms, there was no variation with respect to reports by Zuñiga-Gonzalez, as it was confirmed that the most frequently presented signs are ascending weakness and areflexia and hyperreflexia, a globally common clinical presentation.²⁷ On the other hand, although there were only CFS data from 57.7% of cases, nearly 70% of patients had albuminocytologic dissociation, an amount consistent with previous studies.^32-34

As for the frequency of the electromyographic variants, except for the Asian population, AIDP predominates around the world, with up to 90% of cases.⁸ It should be noted that in our study, AMAN was the most frequent electromyographic variant.

As for treatment, it is important to note that there was no difference in the preference of using plasmapheresis or intravenous immunoglobulin, as this was done following the guidelines proposed by the American Academy of Neurology.³⁵

Finally, our lethality did not differ with respect to that reported in other studies; it is held that even implementing early treatment, approximately 5 to 10% of patients will have death as their outcome, and for those who require mechanical ventilation, mortality is 20%.^15,33 In our case lethality was 11.1%, with a higher percentage in the MFS variant. The explanation may be related to the presence of dysautonomic phenomena, as this was also the variant that presented these the most in the cases analyzed.

Limitations

As a retrospective study, this has limitations by its own nature. Lack of information, lack of uniformity in the diagnostic approach to patients with GBS, an example of which is the lack of results from lumbar puncture. It should however be stressed that the number of patients, when compared to other studies, is large, making it possible to adequately describe the clinical behavior of these patients.

Conclusions

Although there is a classic variant widely described and known in the adult Mexican population, the AMAN variant is the most frequently presented among adults with Guillain-Barré syndrome.

Why our population behaved differently from the rest of the world population and similarly to the Asian population is an unanswered question. It is important to establish better caseloads in our environment and to monitor patients with the disease in the long term.

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