Correlative study between C-reactive protein, clinical severity, and nerve conduction studies in Guillain-Barrè syndrome

Guillain-Barré syndrome (GBS) is a severe autoimmune disorder in which the immune system forms auto-antibodies against healthy nerve cells of the peripheral nervous system causing polyradiculoneuropathy which in turn causes weakness, numbness, and tingling and can eventually cause paralysis. The cause of this condition is unknown, but it is typically triggered by many infectious illnesses like gastroenteritis and respiratory tract infection (Yuki and Hartung 2012). It is generally precipitated 1–3 weeks following many infections like respiratory tract infection and Campylobacter jejuni infection which suggest an underlying humoral immunopathogenic mechanism (Yu et al. 2006).

C-reactive protein (CRP) is an acute phase reactant produced by the liver in response to factors released by macrophages and adipocytes. Its level rises dramatically during inflammatory processes occurring in the body, and it is a critical component of the immune response (Lau et al. 2005), Moreover, CRP plays an important role in innate immunity as an early defense system against infections and its level rises when there is a microbial infection or an inflammation without microbes (Peaceman et al. 1997). Autoimmune conditions like GBS can stimulate the production of a high level of inflammation resulting in an increase in the CRP production, so highly sensitive CRP assay may become a new risk assessment marker in the future for autoimmune disorders including GBS (Vaishnavi et al. 2014). In addition, measuring CRP levels can help to screen both infections and inflammatory diseases; also, dynamic serial measurement of CRP has been widely used to help therapeutic decision making (Lobo 2012).

Electrophysiology including nerve conduction study (NCS) plays a determinant role in GBS diagnosis and classification of the subtypes and in establishing prognosis (Uncini and Kuwabara 2012). Diagnostic sets have been proposed for assessment of acute inflammatory demyelinating neuropathy (AIDP), acute motor axonal neuropathy (AMAN), and acute motor and sensory axonal neuropathy (AMSAN). Nerve conduction studies should be repeated for proper diagnosis of GBS subtypes, identification of pathophysiological mechanisms, and hence assessment of prognosis (Uncini and Kuwabara 2012).

A cross-sectional study was conducted in the Neurology Department, Zagazig University Hospitals during the period from February 2015 to July 2016. Twenty-four patients (10 males, 14 females) which fulfilled the clinical criteria for diagnosis of GBS according to Asbury and Cornblath (1990) were recruited in the study. Their ages ranged from 14 to 50 years with a mean age 33.46 ± 12.25 years.

GBS disability scale (Hughes and Rees 1997)

Nerve conduction studies (NCSs) were done with an EMG machine (Nemus, Biomedica, Model number 00655, Galileo NT software version 3.71/00, Italy) within 2 weeks of onset of symptoms.

The values for each variable were compared with the standard ranges of normality.

A total of 24 GBS cases with ages ranged from 14 to 50 years (mean age 33.46 ± 12.25 years) were included in this cross-sectional study according to the above mentioned inclusion and exclusion criteria.

Guillain-Barré syndrome is a clinically diagnosed disorder, but nerve conduction studies can help to support the diagnosis and discriminate between axonal and demyelinating subtypes and could relate to prognosis (Chiò et al. 2003). C-reactive protein (CRP) is one of acute phase proteins, the serum or plasma levels of which rise during general non-specific response to a wide variety of diseases, either infectious or inflammatory including autoimmune diseases (Lau et al. 2005).

Several studies agree that GBS can occur at any age (Hughes and Rees 1997). In the present study, the mean age of GBS patients was 33.46 (±12.25) years. Our results were in accordance with that obtained by Mohamed et al. (2016), where the mean age of their patients was 38.74 years. However, a higher mean age of 43.7 years was reported by González-Suárez et al. (2013).

Concerning sex distribution, it was reported that GBS was more frequent in females (58.3% females vs 41.7% males) in our study. Other studies found that GBS was more common in male patients (Hughes and Cornblath 2005; Sejvar et al. 2011; Dhadke et al. 2013; Fokke et al. 2014). However, González-Suárezand et al. (2013) in their study found no significant difference between both genders among GBS patients.

Regarding preceding infections in our study, it was found that about 41.7% had gastroenteritis and 25% had URTI while only 33.3% had no history of any infection prior to presentation. These data were in agreement with results obtained by Newswanger and Warren (2004) who identified C. jejuni as the most frequent antecedent pathogen of GBS. Sudulguntaand et al. (2015) in their study found that the most common antecedent events associated with GBS was gastrointestinal infection (47.25%) followed by fever and cough which represented 42.62%, while upper respiratory tract infection was reported to be the most common preceding infection in studies done by Chiò et al. (2003) and Willison (2005).

Patients with Guillain-Barré syndrome differ from each other regarding the degree as well as distribution of motor and sensory symptoms plus the presence of cranial nerve deficits, autonomic dysfunction, and preceding infection. Regarding the clinical presentation, we found that all patients (100%) had both motor and sensory symptoms, while 54.2% had facial nerve involvement, 16.7% had autonomic symptoms, and 16.7% needed MV. Fokke et al. (2014) and Kalita and Misra (2014) reported that motor weakness was the most frequent symptom (73.8–100%) and sensory symptoms represented 52.7% and cranial nerve affection represented 53–62.5%. Other studies (Dhadke et al. 2013; Fokke et al. 2014; Kalita and Misra 2014) found that dysautonomia represented 20.4% and MV was found in 13.1–28%. A low frequency of sensory manifestations (32.5%) was recorded by Dhadke et al. (2013).

The Hughes disability scale was used to assess clinical severity of GBS in our study. 16.7% of our patients were able to walk either without assistance or with help (grades 2 and 3). The majority of our patients (62.5%) were bedridden or chair bound (grade 4) and 12.5% needed mechanical ventilation (grade 5). This was in agreement with data obtained by Parmar et al. (2013) who reported that the majority of their GBS patients were in grade 4 (83.7%). The author explained that the reason for the high frequency of severe disability was the delay in seeking treatment.

Regarding the electrophysiological studies in our GBS patients, we found that mixed axonal and demyelinating polyneuropathy was the most common type (45.8%) followed by demyelinating polyneuropathy (29.2%) and axonal polyneuropathy (8.3%). In accordance with our result, Walling and Dickson (2013) found that multifocal demyelinating polyneuropathy with secondary axonal degeneration was the most common subtype. However, other studies found that demyelinating polyneuropathy was the predominant subtype followed by demyelinating and axonal polyneuropathy (Fokke et al. 2014; Parmar et al. 2013). This variability of subtypes of GBS among countries could be due to different genetic background and environmental exposures (Parmar et al. 2013).

As regards electrophysiological findings of NCSs among our patients, it was also found that F-wave abnormality was the most common finding (70.8%), then prolonged distal latency (DL) (66.7%), low compound motor action potential (CMAP) amplitude (54.2%), and slow conduction velocity (37.5%), and the least was absent motor response (20%). Whereas in sensory nerve conduction studies, prolonged latency as well as reduced SNAP amplitude were the most prominent finding (16.7%). Our results were in agreement with that of Parmar et al. (2013) who found that the most common electrodiagnostic abnormalities were absent or prolonged F-wave (90%), prolonged DL (80%), delayed CV (73%), partial or complete conduction block (63%), reduced CMAP amplitude (38%), and abnormal SNAP (28%). The authors explained the predominance of F-wave abnormalities in GBS patients by an axonal dysfunction in proximal nerve segment or by axonal degeneration at the level of nerve root (Parmar et al. 2013).

C-reactive protein is one of the acute-phase proteins, which rises during a wide range of acute and chronic inflammation (Vaishnavi et al. 2014). Also, CRP has a role in autoimmune diseases as it can bind to auto-antigens; thus, immune-mediated conditions like GBS can stimulate inflammatory response which in turn lead to in an increase in CRP level (Szalai 2004). In the present study, CRP level > 6 mg/dl were found in 33.5% of our patients. This was in agreement with Vaishnavi et al. (2014) who found that 24.4% of their patients were positive for CRP. Although there were few studies concerning CRP serum levels in patients with GBS, a high level of CRP was reported in other studies (Daniel 2011; Chen et al. 2013).

On doing a multivariate regression analysis, it was found that serum CRP level > 6 mg/dl was significantly associated with preceding infection (gastroenteritis), need for MV, disability score > 4, and absent both motor and sensory nerve responses. Our results were in agreement with the study done by Rajabally and Uncini (2012) who found that predictors of bad prognosis were higher GBS disability score at 2 weeks, preceding diarrheal illness, faciobulbar palsy, need for MV, low CMAP amplitude, and absent motor responses. Also, Ortiz-Corredor et al. (2007) studied motor recovery after GBS in childhood, using univariate analysis and found that cranial nerve impairment, requirement of assisted ventilation, presence of quadriplegia, and presence of non-excitable motor nerves were associated with delayed motor recovery time. In explanation for that significant association, Vaishnavi et al. (2014) postulated that autoimmune conditions like GBS can stimulate inflammatory response and hence result in an increase in CRP production which in turn significantly related to clinical severity and severe disability resulting in poor prognosis in GBS patients.

The results of the current study support the hypothesis that in GBS patients, history of preceding gastroenteritis, craniobulbar affection, need for MV, disability score > 4, and absent motor and sensory nerve responses were significantly associated with high serum CRP level, reflecting the negative impact of the inflammatory response on clinical severity and prognosis. Serial measurement of CRP can be used as risk assessment and prognostic marker.