INTRODUCTION

 

Guillain-Barré syndrome (GBS) is an acquired inflammatory demyelinating polyneuropathy¹. It is a distinctive type of autoimmune polyradiculo-neuropathy characterized by subacute onset of symmetrical lower motor neuron paralysis of obscure etiology². However, numerous types of antecedent events as infection, surgery and vaccination were described in association with GBS in more than 70% of cases³. GBS with its acute onset is very heterogeneous because not only the neurological manifestations and severity are highly variable, but also the type of antecedent infection, which is related to anti-ganglioside antibody production, varies⁴.

Guillain-Barré syndrome is the third common cause of peripheral neuropathy after diabetes and leprosy and constitutes the first cause of rapidly developing peripheral neuropathy¹. It is the most common cause of acute flaccid paralysis in the western hemisphere and probably worldwide, with an average incidence of about 1.5 per 100,000⁵. However, the course and prognosis of cases with GBS vary widely⁶. 

The motor and sensory disabilities in patients with GBS tend to be associated with electrophysiological evidence of axonal degeneration. So, the electrophysiological studies can be used in evaluation of the diagnosis as well as the prognosis of patients with GBS⁶.

Approximately, 3-10% of cases with GBS have more relatively sudden relapse⁷. However, very rare cases of GBS die from respiratory muscles paralysis or cardiac arrest if intensive care is not supplied⁷.

The aim of this study was to detect the clinical and laboratory predictors of outcome in patients with Guillain-Barré syndrome.

 

PATIENTS AND METHODS

 

This study was carried out on 24 patients with GBS (14 males and 10 females) recruited from Neuropsychiatry department, Tanta University Hospital. Their ages ranged from 7 to 39 years. The duration of illness at the time of examination ranged from 3 to 12 weeks after the onset. All patients fulfilled the criteria for diagnosis of GBS⁸. Exclusion criteria included patients with diabetes mellitus, tuberculosis, renal disease, hepatic illness, fever, or alcohol abuse. The control group comprised 10 normal volunteers matched for age and sex with the patients group.

 

All patients were submitted to the following:

1-      History taking; (a) The course of the disease was considered progressive if it had been continued to show increased severity of the symptoms and/or the appearance of new symptoms in more than 4 weeks from the onset. It was considered stationary if the clinical manifestations continued at the same level without showing tendency to neither regression nor progression. It was considered regressive if showed a subjective improvement in the clinical manifestations in the last 1-2 weeks before examination. (b) Duration of illness from the onset till time of examination was enquired. (c) History of antecedent illness was obtained.  

2-      General medical examination; for clinical evidence of any cardiac, chest, gastrointestinal, liver or renal disease. Special interest was given to measurement of the blood pressure and pulse rate for any autonomic dysfunction as well as the temperature for exclusion of any infection.

3-      Neurological examination; with emphasis on cranial nerves examination, muscle status and the degree of affection of the motor and sensory systems as well as the deep tendon reflexes.

 

The muscle power was graded according to the Medical Research Council scale (MRC)⁹. Grade 5 (Normal): complete range of motion against gravity and full resistance for 5 seconds. Grade 4 (Good): complete range of motion against gravity with some resistance. Grade 3 (Fair): complete range of motion against gravity. Grade 2 (Poor): complete range of motion with gravity eliminated. Grade 1 (Trace): slight muscle contraction, no joint motion. Grade 0 (Zero): no evidence of contraction.

Assessment of the functional ability by the functional ability score⁹ was done before and after treatment (plasmapheresis and intravenous immunoglobulin) in which the patient was graded by simple objective scale of functional ability (0-6) grades. Grade 0: healthy. Grade 1: minor symptoms or signs. Grade 2: able to walk 10 meters without assistance. Grade 3: able to walk 10 meters with assistance. Grade 4: bed-ridden or chair bound. Grade 5: requiring assisted ventilation for at least a part of day or night. Grade 6: dead. Poor outcome was defined as a functional ability score grade 2 or more. Good outcome was defined as a functional ability score grade less than 2.      

 

4-      Electrophysiological studies, done by the apparatus Nihon-Kohden Neuropack II MEM-7102 A/KO. These studies were carried out in the patients before and 3 months after treatment as well as the controls, and included:

a)      Electromyography, using concentric needle electrodes, done for the right deltoid, abductor pollicis brevis, gluteus maximus and extensor digitorum brevis.

b)      Nerve conduction studies, using 2 small surface electrodes of silver, to record the motor and sensory nerve conduction as well as the F-wave. The motor conduction studies were done for the right median, ulnar and common peroneal nerves. They included the distal motor latency, conduction velocity, the compound muscle action potential (cMAP) and the proximal nerve conduction studies (F-wave latency). The sensory conduction studies were done for the right median, ulnar and common peroneal (deep branch) nerves. They included the distal sensory latency and conduction velocity.

 

Statistical analysis of the data was done using the mean, standard deviation, standard error, the "t" test and the correlation coefficient. Significance was considered when the p value was below 0.05.

 

RESULTS

 

Clinical study:

Patients of the present study were 14 (58.3%) males and 10 (41.6%) females. There was a significant correlation (p<0.05) between the age of the patients and the prognosis; the younger the patients, the better the prognosis. On the other hand, there was no significant correlation between the gender and the prognosis [Table 1].

In the present study, 41.7% of patients with GBS had a regressive course, while 50% had a stationary course and only 8.3% showed a progressive course. Three quarters of patients with GBS had duration of illness from 3 to 7 weeks. Moreover, 79.2% of the patients had a past history of antecedent illness in the form of fever, influenza, upper respiratory tract infection or gastrointestinal disturbance [Table 2].

In the present study, 54.2% of the patients reached maximal weakness within 3 weeks and there was an inverse relationship between the time to maximal weakness and the prognosis [Table 3].

Table [4] showed that 4.2% of patients had passed away due to respiratory failure. These patients had bad prognosis. Patients with sphincter disturbance (8.3%) had a bad outcome. Also, patients with either bradycardia or tachycardia had bad outcome, while only 16.7% of patients with normal pulse rate had bad outcome and 83.3% of them had good outcome. Also, patients with either hypotension or hypertension had bad outcome, while all patients with normal systolic blood pressure had good outcome.

In the present study, 16.7% of the patients with cranial nerve affection in the form of bilateral facial nerve palsy had bad outcome. There was a significant correlation between the presence of muscle wasting and the bad outcome (p<0.05), while the outcome was better in global weakness. Patients with absent deep tendon reflexes in both upper and lower limbs (58.3%) had bad outcome while those with diminished reflexes (41.7%) had good outcome. There was a significant correlation between both the superficial and deep sensory affection and the outcome (p<0.05) [Table 5].

In the present study, there was a significant correlation between grade 2 muscle power in the patients with the bad outcome (p<0.05), as shown in table [6].

In the present study, there was a significant correlation between initial functional ability score and the outcome (p<0.05), as shown in table [7].

 

Electrophysiological study:

In the present study, there was a significant correlation between each of the distal motor latencies of the studied nerves (median, ulnar and common peroneal nerves), the mean amplitude of cMAP on distal stimulation, and the motor conduction velocities of peripheral segments of the three studied nerves and the outcome (p<0.05). On the other side, there was a non-significant correlation between each of the sensory conduction velocities of peripheral segments of the studied nerves and the latencies of F-wave of both ulnar and common peroneal nerves and the outcome (p>0.05), as shown in table [8].

In the present study, there was a non-significant correlation between the distal motor latency, motor conduction velocity and the F-wave latency of the studied nerves (p>0.05), as shown in table [9].

In the present study, there was a significant improvement in the conduction studies of the median, ulnar and common peroneal nerves after 3 months of treatment (p<0.05), as shown in tables [10], [11] and [12].

Table [13] showed the nerve conduction studies in the control group.

 

Table 1. The age and gender relationship with the outcome in patients with GBS.

 

* = significant.

 

Table 2. The distribution of patients according to course, duration and antecedent illness.

 

 

Table 3. The distribution of patients according to the time taken to reach maximal weakness and its relation to the prognosis.

 

Table 4. The distribution of respiratory muscle paralysis, sphincter disturbance, pulse rate and blood pressure in patients and its relation to the prognosis.

 

 

Table 5. The distribution of some neurological data in patients and its relation to the prognosis.

 

 

Table 6. The distribution of muscle power grades in patients and its relation to the prognosis.

 

(P<0.05)

Table 7. The relationship between initial functional ability score and the prognosis.

 

* = significant.

 

Table 8. The relationship between electrophysiological findings and the prognosis.

 

 

Table 9. Correlation between the degree of motor power and other variables in patients with GBS.

 

 

Table 10. The median nerve conduction studies before and after 3 months of treatment in the patients (n=24).

 

* = significant.

 

Table 11. The ulnar nerve conduction studies before and after 3 months of treatment in the patients (n=24).

 

Table 12. The common peroneal nerve conduction studies before and after 3 months of treatment in the patients (n=24).

 

* = significant.

 

Table 13. The nerve conduction studies of the control group.

 

 

 

DISCUSSION

 

The course and prognosis of cases with GBS vary widely from rapid complete recovery to very slowly regressive course with residual deficits in the form of wasting, weakness of distal muscles and joint deformity, persistence of glove and stocking hypoesthesia, ataxia if present from the start and weakness of facial muscles if involved⁶. The present work was concerned with the clinical and electrophysiological predictors of outcome in patients with GBS.

 

Clinical study:

The percentage of complete recovery in the present study was 41.7% in which full clinical recovery was achieved as return to normal activity with normal muscle power and return of deep tendon reflexes. Among the 14 patients with unfavorable outcome, 13 showed incomplete recovery while one passed away due to respiratory muscle paralysis. Most of the studies concerned with the prognosis in patients with GBS reported that favorable course ending with complete recovery occurs in about 60-80% of patients^10-14. The difference might be due to the relatively shorter period of follow up in the present study (3 months). 

The present study revealed that the younger patients had good outcome and the older had bad outcome (p<0.05). This is in agreement with previous reports that revealed children with GBS suffer rare from residual deficits and less mortality as well^15-17. Moreover, incomplete recovery tended to occur with increasing age. A finding that is attributed to the factor of ageing which retards the repair of affected nerves in older patients¹⁸. 

There was no significant correlation between the gender and the outcome in our work (p>0.05). This matches many previous studies ^{(10,11,12,13,14)}. However, many authors recorded slightly higher incidence of occurrence of GBS in males^19,20,10.

In the present study, 54.2% of patients reached maximal weakness within 3 weeks, while 25% reached maximal weakness within 1 week, all of them had bad outcome. This is in substantial agreement with that described by Winer et al.¹⁵, who suggested that the average interval to reach maximal weakness is significantly shorter in those with residual deficits and in those deteriorates rapidly. In contrast to our results, Arnason and Solivan²¹ concluded that patients with GBS who are taking longer period of time to reach their maximal neurological weakness have a more protracted recovery. Also, Bersano et al.¹⁶ concluded that patients reaching maximal worsening within 10 days achieved maximal improvement more quickly and remained less disabled than the others while those with more than 10 days plateau duration remained more severely impaired than those with a shorter duration.

In the present study, one patient had respiratory failure due to respiratory muscle paralysis and died. Previous studies^10,15,22 reported that manifest affection of respiration has an immediate relationship with bad prognosis.

In the present study, only 2 patients (8.3%) with sphincter disturbance had bad outcome. This is going with that reported by Osler and Sidell²³, who concluded that patients with a strictly motor neuropathy without sphincter disturbance are more likely to have a good prognosis.

In the present study, all patients having bradycardia, tachycardia, hypotension and hypertension had bad outcome while only 16.7% with normal pulse rate had bad outcome. This is in agreement with Tuck and McLeod²⁴, who reported that autonomic dysfunction in patients with GBS may manifest as either excessive or inadequate activity of the sympathetic or parasympathetic system causing wide variation in the blood pressure and heart rate. Paroxysmal episodes of increased autonomic activity causing hypertension and tachycardia are associated with poor prognosis. In contrast to our results, Singh et al.²⁵ suggested that the autonomic dysfunction in patients with GBS do not appear to have any prognostic significant difference between good and bad outcome groups of patients. Also, Singh et al.²⁶ found autonomic dysfunction in 66.6% of patients with GBS but were mostly mild or transient and this does not affect the long term results.

In the current work, bilateral facial diplegia was present in 16.6% of patients, all had bad outcome. This is going with Takeuchi et al.²², who reported that multiple cranial nerve affection is associated with bad outcome. There was a significant correlation between the presence of muscle wasting and the prognosis (p<0.05). This is in agreement with that reported by many authors^{10,11,13,14,27}, who reported a significant correlation between muscle wasting and subsequent bad prognosis. Also, there was a significant correlation between motor power in patients with GBS and the prognosis (p<0.05), the severe the degree of muscle weakness, the bad prognosis. This is going with many authors^10,11,14,28, who reported that severe motor deficit appears to carry a greater risk of residual disability and this might reflect the severity of inflammatory response in the nerves.

In the present study, all patients with global weakness had good outcome, while only 28.6% of patients with distal weakness had good outcome. This is in agreement with Winer et al.¹⁵, who concluded that global weakness is associated with good outcome, while severe distal weakness is associated with bad outcome. This might be explained by that the distal muscles are innervated by nerves running along entrapment sites and so having the most severe deficit. Moreover, Visser et al.²⁹ reported that the distal predilection may be associated with a random distribution of demyelination or be the result of primary or secondary axonal involvement so it is associated with bad outcome.

It was found also in the present study that all patients (41.7%) with diminished deep tendon reflexes in upper and lower limbs had good outcome, while patients with absent deep tendon reflexes (58.3%) had bad outcome. This is going with the study of Winer et al.¹⁵ and Rayan³⁰.

In the current work, there was a significant correlation between both the superficial and deep sensory affection and the bad outcome (p<0.05). This is in substantial agreement with many previous investigators^22,15,28. In contrary to our results, Marshall³¹ found patients with sensory loss had no evidence to influence the prognosis adversely.

In the present study, there was a significant correlation between the initial functional ability score and the prognosis (p<0.05). This is going with the study of Winer et al.¹⁵.

 

Electrophysiological study:

In the present study, there was no significant correlation between delay in distal motor latencies of the median, ulnar and common peroneal nerves and the prognosis (p>0.05). On the other hand, there was a significant improvement of the distal motor latencies of the three studied nerves after 3 months of treatment when compared to those at initial assessment (p<0.05). This is in agreement with Raman and Taori³², who reported that the degree of conduction slowing did not correlate with the severity of muscle weakness.

In the present study, there was a significant correlation between the amplitude of cMAP on distal stimulation of the studied nerves in patients with GBS and the prognosis (p<0.05), with significant improvement after 3 months treatment when compared to that at initial assessment (p<0.05). This is in agreement with Cornblath et al.³³, who concluded that the mean distal cMAP amplitude is the single best predictor of outcome regardless of other measures.

In the present study, there was a significant correlation between the motor conduction velocities of peripheral segments of the studied nerves and the prognosis in patients with GBS (p<0.05). This is in agreement with Eisen and Mumpherys¹², who reported that normal electrophysiological results in the acute stage are of good prognostic value, while other authors ^(34,35) reported that gross abnormalities in nerve conduction may not indicate bad prognosis and no correlation exists between the degree of conduction slowing and the clinical outcome in GBS.

In the present study, there was no significant correlation between the sensory conduction velocities of peripheral segments of the studied nerves and the prognosis (p>0.05) with significant improvement after 3 months treatment when compared to those at initial assessment (p<0.05). This is in agreement with Winer et al.¹¹, who reported that many patients have significant slowing of sensory conduction especially later in their illness but not valuable in predicting the outcome.

There was no significant correlation between F-wave latencies of the studied nerves and the prognosis (p<0.05), with a significant improvement after 3 months treatment when compared with those at initial assessment (p<0.05). This is in agreement with other authors^10,32, who reported that F-wave latencies are abnormal in patients with GBS but not adding any predictive value.

In the current work, there was no significant correlation between the motor power on one hand and other variables including the distal motor latencies, motor conduction velocities and F-wave latencies on the other hand (p>0.05).

Although the electrophysiological studies help the diagnosis, the nerve conduction studies show no correlation between the degree of impairment of conduction and maximal clinical disability in patients with GBS. So, patients with segmental demyelination in proximal parts of nerves or in the roots may be severely paralyzed but have normal peripheral nerve conduction velocity. Therefore, minor disability may be present in some patients with GBS having slowing of the conduction velocities³⁶. However, evidence of electrophysiological demyelination may be a predictor of bad outcome³⁷.

 

Conclusion

The clinical predictors of outcome in patients with GBS are the age (the younger the age the more favorable outcome), the mode of onset (attaining maximal deficit in less than 3 weeks carries a bad outcome), and the severity of clinical involvement (manifest respiratory muscle affection, sphincter disturbance, marked autonomic disturbance, cranial nerve affection, marked degree of muscle wasting, severe degree of muscle weakness, absent deep tendon reflexes and the presence of sensory affection; all are associated with bad outcome).

On the other hand, the electrophysiological findings can provide a prognostic value in patients with GBS. Delayed motor conduction velocity and reduced amplitude of cMAP on distal stimulation carry a bad outcome, but other measures including sensory conduction velocity, F-wave response, and distal motor latency have no significant correlation with the outcome.  

 

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