Guillain-Barré Syndrome (GBS) is a rare, immune-mediated disorder characterized by rapid-onset, progressive weakness and areflexia, primarily affecting the peripheral nervous system (1). It is often preceded by an infection, most commonly viral or bacterial. Optic neuritis (ON), a demyelinating condition of the optic nerve, occasionally co-occurs with GBS, presenting an unusual challenge in diagnosis and treatment (2). The co-occurrence of these two conditions is extremely rare, particularly in pediatric populations.

This case report presents the first known pediatric case in China of GBS complicated by bilateral optic neuritis, triggered by an upper respiratory infection. The rarity of this combination, particularly in a child, underscores the complexity of diagnosis and treatment, highlighting the need for timely intervention to prevent severe sequelae. This report aims to contribute valuable insights into the pathophysiology, clinical management, and treatment outcomes of GBS/ON, with a particular focus on the role of rituximab, a drug not commonly used in GBS treatment.

A 14-year-old male presented to the intensive care unit (ICU) at the Second Hospital of Lanzhou University with acute onset of progressive weakness in all four limbs over the preceding half-day. The patient had experienced a week-long upper respiratory infection with fever, for which he self-administered medications without significant improvement. On the night prior to admission, he developed sudden limb weakness with initial ambulation difficulties that did not improve with rest. By morning, he required assistance to walk, with symptoms progressing to include numbness in both feet, dysarthria, generalized muscle pain, and difficulty swallowing. As his condition continued to deteriorate, he was brought to the emergency department, where he experienced worsening weakness and difficulty breathing, requiring immediate ICU admission. Serological tests and PCR tests were done in the emergency room, but the results were negative.

Upon admission, his vital signs included a body temperature of 36.5°C, respiratory rate of 29 breaths per minute, pulse of 111 beats per minute, and blood pressure of 128/76 mmHg. Respiratory examination revealed coarse breath sounds with wet rales in both lungs. Neurological examination showed preserved consciousness but reduced alertness, slurred speech, bilateral pupil dilation with prompt light reflexes, full range of eye movement without nystagmus, and decreased muscle tone in all four limbs. Proximal muscle strength was graded as 2/5 in both upper limbs and 1/5 in the lower limbs, with absent deep tendon reflexes and a negative Babinski sign bilaterally.

Following diagnosis, the patient was immediately admitted to the ICU and placed on mechanical ventilation. Intravenous immunoglobulin (IVIG) therapy was initiated at 0.4 g/kg/day for five consecutive days. Given the concurrent optic neuritis (ON), the clinical diagnosis was confirmed as Guillain-Barré syndrome with optic neuritis (GBS/ON). On the fourth day of IVIG treatment, high-dose methylprednisolone (500 mg/day for five days) was added, followed by tapering to 250 mg/day for five days and subsequently 120 mg/day for three days. The patient was then transitioned to oral methylprednisolone, initially dosed at 60 mg and tapered by 4 mg weekly, maintaining a low-dose regimen of 8 mg/day for long-term use.

Despite these interventions, the patient’s condition did not improve significantly after the initial course, with persistent quadriplegia and respiratory muscle weakness. Additionally, he developed a severe pulmonary infection, requiring tracheostomy and intensive antimicrobial therapy. Sixteen days post-IVIG, a trial of rituximab was administered given the absence of notable recovery, especially in motor strength. This led to a gradual improvement in muscle strength, with follow-up assessments showing strength gains in the upper limbs (proximal strength 2+, distal strength 1) and partial strength in the lower limbs.

Over the subsequent weeks, a second round of IVIG therapy (0.4 g/kg/day for five days) resulted in further functional improvement. The patient regained partial visual acuity in the right eye (50 cm finger-counting) and left eye (0.03 visual acuity), with color differentiation restored. On the 47th day of treatment, the patient was successfully weaned off mechanical ventilation, transitioning to autonomous breathing. After two months, he demonstrated significant recovery with muscle strength graded between II and III, visual acuity improved to 0.06 in the right eye and 0.04 in the left eye, visual evoked potentials showed a delay in P2 peak in both eyes, ( Table 3 ).Optical coherence tomography (OCT) showed persistent retinal nerve fiber layer thickening and optic disc pallor ( Figure 2 ). Enabling transfer from the ICU to the rehabilitation unit.

In rehabilitation, targeted therapies included physical exercise, physical agent modalities, hyperbaric oxygen, and nerve growth factor injections, along with vitamins B1 and B12. Visual function further improved as confirmed by ophthalmological assessments. After three months, the patient was discharged with muscle strength restored to grades IV and V, achieving near-independence in daily activities. At present, the patient has been ill for six months, and we have recently followed up and found that his motor function and color discrimination had fully recovered. But the level of vision has not fully recovered, the vision in the left eye was 6/24, and the vision in the right eye was 8/24. The patient was able to perform daily activities independently ( Table 4 ).

This case presents a rare co-occurrence of GBS and bilateral optic neuritis (GBS/ON), a combination that has been infrequently reported, especially in pediatric patients. While GBS is typically associated with peripheral nerve involvement, optic neuritis represents an uncommon, central nervous system manifestation. The pathophysiology of this dual involvement suggests a systemic autoimmune response that targets both central and peripheral myelin.

Our systematic review identified 33 prior GBS/ON cases. As of July 2024, 24 articles have been published worldwide, reporting cases of GBS combined with ON (3–27), with pediatric cases being particularly rare. Internationally, only three pediatric cases have been reported (4, 27) ( Table 5 ). This case, involving a 14-year-old patient treated at the Second Hospital of Lanzhou University with GBS/ON, represents the first reported pediatric case in China. Including this case, there are a total of 34 cases, with a male-to-female ratio of 1:1. The majority of cases involve middle-aged adults, with a median onset age of 43 years (range: 7–72 years). Optic neuritis predominantly affects both eyes (24 out of 34 cases). Among the 34 cases, 12 exhibited simultaneous onset of GBS and ON, and 24% had respiratory muscle involvement.

The pediatric case we report has the following novel aspects compared to the three previously reported pediatric cases: The patient rapidly developed quadriparesis and respiratory failure, requiring mechanical ventilation, with poor response to standard treatments (IVIG and corticosteroids).Rituximab was introduced during treatment, leading to gradual recovery of motor and visual functions, marking the first report of its use in GBS/ON. The simultaneous occurrence of GBS and optic neuritis (ON) suggests that the immune response may target both the peripheral and central nervous systems, highlighting potential immune cross-reaction. This is the first reported pediatric case in China of a 14-year-old male with co-occurring GBS and ON, offering new insights into the clinical management and treatment of this rare complication.

Previous reports have documented the coexistence of GBS with conditions like acute disseminated encephalomyelitis, transverse myelitis, multiple sclerosis, and ON (28). GBS combined with transverse myelitis is the most commonly reported syndrome, whereas GBS/ON is rarely reported (29). These cases are often associated with various infections, with most GBS cases having a history of antecedent infection, including cytomegalovirus (CMV), Epstein-Barr virus (EBV) (30), measles (31), and Mycoplasma pneumoniae, the most common antecedent pathogen in GBS (32). In one pediatric study, 7% of children with GBS had prior Mycoplasma pneumoniae infection (33). There have been reports suggesting that Mycoplasma pneumoniae can trigger isolated optic neuritis (34). Among GBS/ON cases, Mycoplasma pneumoniae is also the most common antecedent pathogen, though the causal relationship between Mycoplasma pneumoniae and autoimmune diseases remains unclear. Shared immune mechanisms, such as molecular mimicry, may have triggered concurrent demyelination in both the peripheral and central nervous systems. Additionally, whether GBS/ON represents an overlap syndrome or a continuous pathological process remains unclear (35). This patient had a history of antecedent infection with fever one week before onset. Unfortunately, pathogen testing was not performed before onset. Although serological and PCR testing for pathogens were negative, the preceding upper respiratory infection raises the possibility of molecular mimicry contributing to systemic autoimmunity. This mechanism may explain the simultaneous peripheral (GBS) and central (ON) nervous system involvement.

The sequential onset of quadriparesis and optic neuritis suggests a continuous pathogenesis involving shared autoimmune mechanisms targeting central and peripheral myelin. The absence of other CNS lesions on MRI ruled out conditions like multiple sclerosis and ADEM.

Visual impairment followed motor symptoms by one day, supporting the hypothesis of a systemic immune-mediated process. The absence of pain on eye movement suggests a non-ischemic inflammatory mechanism.

This case highlights the importance of co-existing GBS and ON in influencing treatment decisions. For GBS, plasma exchange (PE) or intravenous immunoglobulin (IVIG) is the primary treatment, while glucocorticoids may exacerbate muscle weakness due to steroid myopathy (36). However, glucocorticoids are also the main treatment for ON (37). Despite high-dose glucocorticoid and immunoglobulin therapy, the patient’s condition deteriorated rapidly to a state of quadriplegia and blindness, lasting approximately four weeks. Rituximab has been considered effective for central and peripheral nervous system diseases but has been associated with serious adverse events (38, 39).

There are no prior reports of Rituximab use in GBS/ON. This patient received multiple immunotherapies, including Rituximab, after no significant symptom relief was observed following initial IVIG and steroid treatment. The decision to initiate rituximab was based on the lack of response to initial treatments, and its introduction led to significant improvement in both motor strength and visual function, rituximab was chosen due to its targeted action on B cells, which play a central role in the pathogenesis of both GBS and optic neuritis. Alternatives like tocilizumab or oral immunosuppressants may be considered for future comparative studies. However, given the use of multiple immunosuppressants, the role of Rituximab in recovery remains uncertain. This pediatric case of GBS/ON highlights potential contradictions in clinical treatment. The complexity and severity of the condition posed significant treatment challenges, yet favorable outcomes were still achievable despite severe disease progression and prolonged course.

This case underscores the complexity of managing Guillain-Barré syndrome with optic neuritis (GBS/ON), particularly in pediatric patients with severe presentations. The overlapping central and peripheral autoimmune manifestations posed unique diagnostic and therapeutic challenges, necessitating a multidisciplinary approach. Future research should focus on the underlying mechanisms linking GBS and ON, exploring whether these represent overlapping syndromes or distinct manifestations of systemic immune dysregulation. Establishing standardized treatment protocols for such rare cases is crucial to optimize outcomes and guide clinical practice.