Recurrence of Guillain Barré Syndrome in Patient Pediatric with Presentation of Two Different Clinical Variants

Abstract

Guillain Barré Syndrome (GBS) is an acute demyelinating polyradiculoneuropathy, with unusual heterogeneous clinical variants in pediatrics. There may be infection prior to the clinical manifestations of GBS. Establishing a diagnosis and treatment is challenging. In the present work, a 7 year old schoolgirl is presented, healthy, without risk factors, with recurrence on 2 occasions with different clinical variants of GBS. The 1st episode of GBS was 2 years old, with a history of respiratory infection. Debuting later with clinical manifestations of acute inflammatory demyelinating variant GBS. During her hospital stay, she received treatment with intravenous immunoglobulin (IVIG) (dose of 1grkg for 2 days), without respiratory and/or bulbar compromise, being discharged and sent to rehabilitation to continue multidisciplinary management. The 2nd episode of GBS was at 7 years, I presented recurrence of acute axonal motor variant GBS, secondary to respiratory infection, with acute evolution and respiratory failure, bulbar involvement, areflexia and dysautonomias, requiring mechanical ventilation for 37 days, administering IVIG of 1 grkg for 2 days). During the hospital course there was a serious neurological condition, with gradual improvement, discharging with a tracheostomy, without supplemental oxygen, tolerating the oral route and sent to neurological rehabilitation and otorhinolaryngology to reduce subsequent sequelae.

1. Introduction

Guillain Barré Syndrome (GBS) is an acute demyelinating polyradiculoneuropathy, of autoimmune origin, which presents with various heterogeneous clinical variants [1]. In most cases there is an infectious picture prior to the clinical manifestations of GBS (acute paralysis, weak limbs and inability to ambulation) [1, 2].

In 1857, Landry described the first cases of GBS. The affected patients presented with predominantly ascending motor paralysis, respiratory failure and death [3, 4]. In 1916, Guillain - Barré Strol [4] demonstrated that these patients presented motor deficits and areflexia, but without sensory affection and with albuminocytological dissociation as part of the integral diagnosis of the SGB [4].

In 1990, Asbury and Comblath established the electrodiagnostic criteria for GBS, characterized by a delay in the conduction velocity of two or more motor nerves [5].

At present, GBS is the most frequent cause of flaccid paralysis in previously healthy children [6]. Worldwide, the annual incidence is 0.6 to 2.4 cases per 100,000 inhabitants, in any age group, affecting both genders with an H relationship./M 1.5: 1 [7].

The main infectious agent reported in outbreaks of GBS is C. jejuni [8]. Other infections associated with GBS are: cytomegalovirus (CMV), Epstein–Barr virus, Influenza A virus, Mycoplasma pneumoniae and Haemophilus influenzae [9].

GBS is defined clinically, pathologically, and electrophysiologically as an acute inflammatory demyelinating polyneuropathy. According to the characteristics of the nerve conduction studies, it was observed that GBS is characterized by; slowing of conduction speeds, conduction block, delayed latencies and/or scattered responses; but over time, the evidence from several studies indicated that there are different clinical, serological, and electrophysiological characteristics in each of the GBS variants.

The following describes in detail the pathophysiology and clinical picture that characterizes each of the GBS variants:

1. In the variant of the Acute Inflammatory Demyelinating type (PDIA); there is involvement of the motor roots [10], segmental demyelination, infiltration of mononuclear cells, predominantly T lymphocytes and macrophages in the peripheral nervous system, chains of sympathetic ganglia and cranial nerves [11]. In addition to proliferation of Schwann cells as part of the repair mechanism. There is an antibody cross-reaction against ganglioside GM1, finding axonal epitopes similar to gangliosides present in Campylobacter jejuni (serotypes 019 and 041), whose polysaccharides are similar to gangliosides located in the nerve, this being the explanation for direct axonal damage and demyelination [12]. The main symptom is symmetrical weakness in the lower extremities, decreased or absent deep tendon reflexes (areflexia) and localized pain in the lower extremities or low back pain, present in 79% of the reported trials [13].

2. In the Miller Fisher Syndrome (SMF) type variant; the clinical findings are very similar to those present in Acute Inflammatory Demyelinating. The main culprit is ganglioside GQ1b [14], located in the myelin of cranial nerves, the main ganglioside damaged by specific cross-reactive antibodies caused by Campylobacter jejuni infections. The ganglioside GQ1b is considered a marker of ophthalmoplegia in GBS [15, 16]. The anti-GT1 antibody is also a marker of compromise and translates bulbar cranial nerve damage in GBS [17]. The classic triad of MFS is: ataxia, areflexia and ophthalmoplegia. About 50% of the cases have been reported as the first clinical condition diplopia and/or facial paresis. In the case of external ophthalmoplegia very characteristic of SMF, the first muscle affected is the superior rectus muscle, followed secondarily by lateral rectus muscle paralysis and finally the inferior rectus muscle is affected. Bell’s phenomenon is common in patients with MFS [18].

3. In the Axonal type variant; no inflammatory changes are seen, only a discrete primary lesion is found at the level of the nodes of Ranvier, explaining the axonal degeneration. The anti-GD1a antibody is specific for this variant [19]. The clinical picture is not severe and depends on the extent of axonal injury. Regarding the clinical examination of the patient, the tendon reflexes are preserved and he may even have hyperreflexia. Distal limb involvement shows rapid and complete recovery [18, 20]. Therefore, regardless of GBS variants, axons are the main target for autoimmune injury [21].

Regarding medical treatment, the effect of immunotherapy in GBS has been studied for many years (mainly in studies of randomized controlled trials), establishing that the use of intravenous immunoglobulin (IVIG) and plasma exchange (plasmapheresis) they are effective [22]. The cornerstone of GBS treatment in pediatric patients is based on the use of intravenous immunoglobulin. The treatment can be applied in 2 different therapies; 1st therapeutic (most effective): immunoglobulin dose (2 gr/kg of body weight) administered in two days at 1 gr/kg per day. The 2nd therapy: dose of immunoglobulin at 0.4 gr/kg of body weight administered in 5 days [2, 23].

The specific indications for the use of IVIG in GBS are; rapid progression of muscle weakness, respiratory failure or ventilatory mechanical support, involvement of the bulbar or cranial nerve and inability to ambulation [2]. Plasmapheresis has shown the same efficacy as immunoglobulin but constitutes a more invasive treatment, being reserved only for cases of intolerance or poor response to intravenous immunoglobulin administration [24].

The severity of the clinical picture is important as a prognostic factor in GBS. About 40% of affected children have an inability to ambulate during the acute phase. In severe cases, approximately 25% of patients will require special supports in Intensive Care Units due to the need for support with artificial ventilation secondary to dysautonomias [12, 25, 26, 27].

The authors present the case of a 7 year old girl with severe and atypical Guillain Barré syndrome, describing the clinical course and associated complications in a recurrence of GBS in pediatrics.

2. Presentation of clinical case

7 year old female. Healthy mother and father. No hereditary diseases. Surgical, traumatic, transfusion, allergic, rash history questioned and denied. Complete vaccination schedule according to age.

3. Hospitalizations

3.1 1st hospitalization

At 2 years of age due to acute inflammatory demyelinating variant Guillain Barré syndrome. In September 2012, GBS was diagnosed secondary to an upper respiratory tract infection 1 week prior to admission, with partial improvement in infection after administration of antimicrobials and antipyretics for 3 days. Later clinical symptoms of GBS characterized by weakness in both lower extremities were added, going to the emergency room. Upon admission to the emergency room, she found normal vital signs; HR 116/minute, FR 30/minute, Temp 36 °C, oxygen saturation 93%. Physical examination: female of apparent age similar to chronological age, adequate hydration, normocephalic skull, oral cavity with grade II tonsillar hypertrophy and hyperemic pharynx, neck without megalia, cardiopulmonary without compromise, soft abdomen without megaly or peritoneal irritation, upper extremities; eutrophic, conserved strength 5/5 on the Daniels scale, conserved tendon reflexes, pain withdrawal and conserved sensitivity, lower extremities; eutrophic, strength reduction 3/5 on the Daniels scale, bilateral areflexia, withdrawal to pain and preserved sensitivity. Neurological: awake, reactive to external stimuli, non-measurable gait, preserved sensitivity, preserved cranial nerves, absent meningeal signs, no neurological deterioration or dysautonomias.

3.1.1 Hospital clinical evolution

Day 1. Laboratories. Hematic biometry: leukocytes 6,800 leu/μl, neutrophils 27%, lymphocytes 62%, monocytes 8%, hemoglobin 13.6%, hematocrit 40.3%, platelets 482 thousand, CRP 0 mg/dl, CPK 737 U/l. Seric electrolytes: sodium 138 meq/l, potassium 4.9 meq/l, chlorine 105 meq/l, calcium 11.1 mg/dl, phosphorus 6.2 mg/dl, magnesium 2.3 mg/dl. Blood chemistry and kidney function tests: glucose 70 mg/dL, BUN 22 mg/dL, Urea 47 mg/dL, creatinine 0.3 mg/dl. Lumbar puncture: clear, colorless, transparent liquid, 1 cells, 100% monocytes, negative erythrocytes, glucose 43 mg/dl, chloride 118.3 meq/L, proteins 57 mg/dl, pandy positive (+), pH 7.6, lactate 1.6, no bacteria, negative coagglutination. Medical treatment was started with intravenous immunoglobulin (IVIG) at a dose of 1 gr/kg for 3 days.

Day 2. Neuroconduction study: acute inflammatory demyelinating variant GBS (see Figure 1).

Figure 1.

Neuroconduction study (female 2 years).

Day 3. Negative cerebrospinal fluid culture. Negative peripheral blood culture.

Day 6. During his hospital stay, he presented adequate evolution, with gradual improvement in the mobility of the lower extremities; strength 4/5, bilateral areflexia, preserved sensitivity, no secondary complications, tolerating the oral route, no respiratory distress, without requiring ventilatory support, deciding his discharge with wheelchair support and sent to pediatric rehabilitation for 6 months with clinical improvement.

3.2 2nd hospitalization

7 year old female. Condition: 3 day history of upper airway infection with torpid evolution despite established medical treatment, adding paresthesias of the lower limbs with ascending, progressive and symmetrical spread, extending to the upper limbs and poor management of bronchial secretions, therefore which, goes to the emergency service for assessment. Upon admission to the emergency service, she had stable vital signs; HR 95/minute, FR 14/minute, oxygen saturation 93%, temperature 36.5 °C. Physical examination: female of apparent age similar to the chronological one, adequate hydric status, full oral cavity without alterations, neck without megaly, cardiopulmonary without compromise, abdomen without megaly, no data of peritoneal irritation, upper extremities; eutrophic, strength decreased 1/5 on the Daniels scale in the left upper limb and 2/5 in the left upper limb, bone tendon reflexes abolished and sensitivity preserved, lower limbs; eutrophic, decrease in strength 0/5 on the Daniels scale, bilateral areflexia, non-withdrawal of pain and preserved sensitivity. Neurological: awake, reactive to external stimuli, no palpebral ptosis, normoreflectic isochoric pupils, normal bilateral fundus, preserved cranial nerves, preserved superior mental functions, non-assessable gait, non-assessable romberg signs, preserved sensitivity, absent meningeal signs, no dysautonomias.

Guillain Barré Syndrome was diagnosed, for which it was decided to prescribe hydroelectrolytic treatment with solutions to basal requirements by the Hollidey-Sigar formula.

3.2.1 Hospital clinical evolution

Day 1. During her first hours in the emergency service, she presented acute respiratory distress, which is why advanced management of the airway was decided and she was admitted to the Intensive Care service, starting an infusion of Midazolam at 100 mcgkghr. Laboratories Hematic biometrics: leukocytes 14,140 leu/μl, neutrophils 59.6%, lymphocytes 29.7%, hemoglobin 14.8%, hematocrit 44.2%, platelets 434 thousand, ESR 20 mm/h, PCT <0.5 ng/ml, CRP <0.5 mg/L. Liver function tests: BT 0.37 mg/dl, BD 0.11 mg/dl, BI 0.26 mg/dl, TGO 34 IU/L, TGP 21 IU/L, GGT 9 IU/L, CK 28.9 IU/L, CK-MB 28 IU/L. Blood chemistry and kidney function tests: glucose 96 mg/dL, urea 34 mg/dL, BUN 16 mg/dL, creatinine 0.38 mg/dL.

Pediatric Neurology Assessment. Neurological examination with patient under sedation with hyporeflexic isochoric pupils, with a tendency to miosis, facial symmetry, motor with force in the upper extremities proximal 2/5 and distal 1/5 (assessed prior to sedation), lower extremities proximal force and distal 0/5 REM triceps and biceps decreased, bilateral absent patellar and achilleum, non-clonus flexor plantar response, preserved sensitivity, pain withdrawal, rest apparently normal. Patient with clinical evolution of GBS with rapid progression to compromise at the level of the respiratory and bulbar muscles as a poor prognostic factor, therefore, it was decided to start intravenous immunoglobulin at a dose of 1 grkg for 2 days. Lumbar puncture: clear, colorless, transparent liquid, 2 cells, 60% monocytes, negative erythrocytes, glucose 54 mg/dL, chloride 110 meq/L, proteins 103 mg/dL, pandy positive (+), pH 7.6, lactate 1.4, no bacteria, negative coagglutination. Simple and contrasted CT of the skull: without structural alterations and/or abnormal reinforcements. Chest X-ray: no bone structural alterations, no atelectasis, consolidation or pneumothorax.

Day 2. During her 2nd day, she presented a quantified fever>38 degrees Celsius with previous laboratories within normal parameters, but antimicrobial therapy was decided with a double antimicrobial scheme with Cefotaxime and Vancomycin. Neuroconduction study is requested. Study report: abnormal suggestive of GBS with axonal component (see Figure 2). After obtaining a neuroconduction study, medical treatment was started with intravenous immunoglobulin (IVIG) at a dose of 1 gr/kg for 2 days.

Figure 2.

Neuroconduction study (female 7 years old).

Day 7. For 7 days in the intensive care service, she was maintained with ventilatory mechanical support with orotracheal intubation, with poor clinical motor evolution and absence of spontaneous respiratory movements as well as protective reflexes of the airway, therefore, due to the condition neurological, it was decided to perform a tracheostomy to avoid subsequent complications.

Day 8. Sedation based on Midazolam is withdrawn, and analgesic treatment with Ketorolac and paracetamol is continued, without complications.

Day 11. Patient establishes poor verbal communication and begins oral intake based on clear liquids with adequate tolerance. Cough reflex absent.

Day 17. Concludes double antimicrobial regimen with Cefotaxime and Vancomycin (15-day regimen).

Day 19. Progression of oral feeding with a polymeric diet and later a soft diet with adequate tolerance.

Day 23. Food based on a normal diet without eventualities. Gradual evolution with clinical improvement in mobility of the right upper limb and shoulder girdle.

Day 33. Increased mobility of the right hand, left hand, feet in dorsoflexion, and pronosupination.

Day 38. Increased mobility of the bilateral shoulder girdle and hip.

Day 39. Female patient who deserved mechanical ventilatory support for 39 days, progressing with gradual clinical improvement, deciding on a programmed withdrawal of the ventilator without complications, continuing with medical treatment with pulmonary physiotherapy, gentle aspiration of secretions if necessary and supplemental oxygen support, with no evidence of respiratory distress.

Day 40 - Day 43. Multidisciplinary treatment with neurological and pulmonary rehabilitation, education to a family support network for management and care of tracheostomy. Neurological examination: favorable evolution, strength 2/5 on the Daniels scale in the upper extremities, strength 0/5 on the Daniels scale in the lower extremities (Hughes IV Scale - patient confined to bed or chair without the ability to walk), no compromise respiratory, preserved brain stem reflexes. Laboratories: results are collected as part of the GBS protocol in pediatric patients with IgM AC. Anti - Helicobacter Pylori, negative report.

Patient who presented gradual clinical improvement, which is why he was discharged home with a tracheostomy, without supplemental oxygen, tolerating oral route. It is sent for evaluation and follow-up by the neurological rehabilitation and otorhinolaryngology service for medical follow-up due to underlying pathology.

4. Discussion

The recurrence of GBS in pediatrics is rare, as well as the presentation of two clinical variants, which presented different clinical course and remission, despite receiving adequate treatment with intravenous immunoglobulin at a dose of 1 grkg. As previously mentioned, during the 1st episode with acute inflammatory demyelinating variant GBS, the patient presented remission of clinical symptoms without respiratory compromise. But this is not the same way in the 2nd episode of GBS, acute axonal motor variant, where it progresses with acute, torpid neurological evolution, with respiratory and bulbar involvement, meriting phase III ventilation and tracheostomy programming as a protective measure of airway and deficit motor in all 4 extremities for 5 weeks with gradual improvement. Upon discharge, the patient with great limitation to daily activities, staged according to the Hughes Scale in grade IV, found herself confined to bed and requiring the use of a wheelchair to perform daily activities, due to the involvement and motor involvement in the extremities lower, continuing with neurological rehabilitation to delimit the severity of the sequelae.

At present, it is rare to find a case of RGBS, this case being one of the few presentations with an axonal phenotype in a child.

Therefore, it is important for clinicians to recognize the various features of RBGS in recurrence [28].

Remembering that patients may present similar symptoms, but have different findings in the examination, clinical course and electrodiagnostic studies [28, 29].

RGBS may be an underdiagnosed and underrecognized entity in pediatric patients that deserves further study with regard to epidemiology and pathophysiology.

5. Conclusion

Guillain Barre syndrome is a neurological disease that occurs favorably in most cases, but there are clinical variants that can be life threatening, being considered an emergency in pediatrics. The case report shows the importance of the clinical correlation and neuroconduction study to confirm the diagnosis of GBS at an early stage, allowing in turn to initiate the ideal treatment with intravenous immunoglobulin (IVIG) in a timely manner (especially in the most severe GBS), as established in the international guidelines for the diagnosis and treatment of GBS. As established in the literature, mortality from GBS corresponds to less than 5% of cases, but there is a close increase between 15–30% in patients requiring mechanical ventilation. The clinical course of GBS in pediatrics turns out to be more favorable and benign compared to that in adults. Remember that avoiding the mostly associated clinical complications (pneumonia, sepsis, pulmonary embolism, respiratory paralysis, dysautonomias) influence the prognosis of GBS.

Carrying out a prevention and control of possible hospital infections during the evolution of GBS, through adequate care of the airway, conscious use of antibiotics, strict and continuous monitoring, will allow to delimit the sequelae and subsequent complications due to the underlying pathology, making emphasis on physical rehabilitation therapy and adequate nutritional intake.