Pediatric Guillain‐Barré Syndrome Post Organ Transplant: Acute and Chronic Complication Requiring High Index of Suspicion

ABSTRACT

Background

Guillain‐Barré syndrome (GBS) is an acute, immune‐mediated polyradiculoneuropathy most often triggered by infections such as Campylobacter jejuni , Epstein–Barr virus (EBV), or cytomegalovirus (CMV). Although transplant‐associated GBS is recognized in adults, it remains rare in pediatric recipients, and distinguishing immune‐mediated disease from medication toxicity or critical illness can be challenging.

Methods

We describe two pediatric cases of GBS following organ transplantation, one after liver transplant and one after small bowel transplant. Clinical features, diagnostic evaluation, immunosuppression exposure, electrodiagnostic findings, imaging, and treatment outcomes were reviewed to characterize presentation patterns and diagnostic challenges.

Results

The first patient developed rapidly progressive weakness shortly after liver transplantation in the setting of organ failure, adenovirus infection, and transient supratherapeutic tacrolimus levels. She demonstrated severe motor axonal involvement on nerve conduction studies and elevated neurofilament light chains, improving after intravenous immunoglobulin (IVIG). The second patient, years after small bowel transplantation complicated by chronic immune dysregulation and EBV viremia, presented with ascending weakness, areflexia, elevated CSF protein, and MRI enhancement of cauda equina and cranial nerves. Electrodiagnostics confirmed demyelinating polyneuropathy. Symptoms improved after IVIG despite concurrent tacrolimus level elevation. Across both cases, infectious triggers, immunosuppression, and critical illness obscured early recognition.

Conclusion

GBS is an uncommon but important cause of acute weakness in pediatric transplant recipients. These cases show that GBS can occur both early and late after transplantation and may mimic medication toxicity or other complications. Early consideration of GBS, timely electrodiagnostic testing, and prompt immunotherapy are essential for optimizing outcomes in these patients.

Abbreviations

AChR

acetylcholine receptor

AIDP

acute inflammatory demyelinating polyradiculoneuropathy

AV

arteriovenous

CMV

cytomegalovirus

CSF

cerebrospinal fluid

DIC

disseminated intravascular coagulation

DVT

deep vein thrombosis

EBV

Epstein–Barr virus

EMG

electromyography

GBS

Guillain‐Barré syndrome

GM1

monosialotetrahexosylganglioside

GQ1b

ganglioside Q1b

HSCT

hematopoietic stem cell transplantation

IVIG

intravenous immunoglobulin

LP

lumbar puncture

MRI

magnetic resonance imaging

MUSc

muscle‐specific kinase (anti‐MuSK antibody)

NCS

nerve conduction studies

PTLD

post‐transplant lymphoproliferative disorder

SOT

solid organ transplant

1. Background

Guillain‐Barré syndrome (GBS) is an acute, immune‐mediated polyradiculoneuropathy characterized by rapidly progressive weakness, areflexia, and potential respiratory compromise [1]. GBS is a rare condition, with 3000–6000 cases reported annually in the United States [1]. In the pediatric population, the estimated incidence ranges from 0.5 to 1.5 cases per 100 000 children [2]. While the majority of cases are preceded by infections such as Campylobacter jejuni , Epstein–Barr virus (EBV), or cytomegalovirus (CMV), GBS has also been described in the context of immune dysregulation, such as with use of immunosuppressive medication. Medications implicated include antithymocyte globulin and tacrolimus [1, 3, 4, 5, 6, 7]. The understanding of GBS pathophysiology involves molecular mimicry between lipooligosaccharides on bacterial membranes and gangliosides in peripheral nerve myelin, leading to antibody‐mediated demyelination [1].

GBS is primarily diagnosed based on clinical features; progressive, symmetrical limb weakness with diminished or absent reflexes and supported by diagnostic tests. Nerve conduction studies typically show demyelination with slowed conduction velocities or conduction block, while cerebrospinal fluid (CSF) analysis often reveals albuminocytologic dissociation (elevated protein with normal white cell count). MRI of the spine may show nerve root enhancement but is mainly used to rule out other causes. Treatment focuses on halting immune‐mediated damage using intravenous immunoglobulin (IVIG) or plasmapheresis, both of which shorten recovery time when started early. Supportive care, including respiratory monitoring and physical therapy, is crucial for managing complications and promoting recovery [1].

Transplant‐associated Guillain‐Barré syndrome (GBS) has been reported predominantly in adults following both solid organ and hematopoietic stem cell transplantation, whereas pediatric cases remain exceedingly rare. In children, GBS has been described primarily after hematopoietic stem cell transplantation (HSCT), with only isolated reports following solid organ transplantation, most commonly in association with cytomegalovirus (CMV) infection [8]. Across pediatric transplant types, CMV frequently appears as a precipitating factor. Early literature includes a report of a 13‐year‐old who developed GBS shortly after liver transplant, underscoring the rarity of this complication in the immediate postoperative period [9]. In this case, no infectious trigger was identified, and the authors proposed that the transplant surgery itself or the post‐transplant immune dysregulation related to immunosuppression may have precipitated the development of GBS.

A more recent report describes kidney transplant–associated GBS in an 8 year old male secondary to primary CMV infection, reinforcing CMV's role in the early post‐transplant period, a well‐recognized window for CMV reactivation and disease [10]. Broader organ transplant reviews further confirm this pattern, noting that most cases of transplant‐associated GBS occur within 1–6 months post‐transplantation and frequently coincide with recent or active CMV infection [11].

In pediatric HSCT recipients, GBS remains uncommon but well documented. A landmark series reported three children who developed GBS shortly after allogeneic transplantation, implicating both conditioning‐related immune perturbation and post‐transplant immune dysregulation as possible mechanisms [12] (see Table 1).

TABLE 1.

Summary of reported GBS cases following solid organ transplant in pediatrics.

Year	Age	Organ	Citation	Trigger	Treatment/Outcome
2003	13	Liver	Ruiz Domínguez JA, Delgado Domínguez MA et al. Síndrome de Guillain‐Barré después de trasplante hepático pediátrico. Med Intensiva. 2003; 27(6): 430–433 [9].	No definitive trigger identified. Authors propose that the surgery itself and/or immune dysregulation related to immunosuppression (including tacrolimus) may have precipitated the autoimmune response leading to GBS.	Physiotherapy/supportive care. After 12 months, the patient had partial recovery of lower‐extremity strength, persistent steppage gait, and improvement in paresthesias, but recovery was incomplete.
2024	8	Kidney	Lopes DSG, Araujo IO, et al. Guillain‐Barré Syndrome Secondary to Cytomegalovirus Infection in a Pediatric Kidney Transplant Patient. Brazilian Journal of Transplantation. 2024; 27: e4124 [10].	Donor‐derived CMV infection (D+/R−)~2 months post‐transplant	IVIG and antiviral therapy with neurological recovery.
2025	6	Heart	Gross M, Berger R, Neunhoeffer F, et al. Case Report: Post‐surgical Guillain‐Barré syndrome as a rare differential diagnosis of flaccid paralysis of the lower extremities in an infant after cardiac surgery. Front. Pediatr. 13: 1610035 [13].	Reactivation of CMV infection	IVIG and antiviral therapy; poor outcome at 6 months with severe distal weakness and sensory loss.

Subsequent reviews have described post‐transplant GBS as a rare peripheral nervous system manifestation of autoimmune spectrum following allogenic HSCT, mostly associated with infection or other immune complications [14].

Proposed mechanisms for post‐transplant GBS include immune reconstitution phenomena and viral reactivation [10, 11]. GBS‐like syndrome, with ascending paralysis can follow neurotoxicity from immunosuppressive agents such as tacrolimus [5]. The differential diagnosis is broad and includes critical illness neuropathy, nutritional deficiencies, and calcineurin inhibitor‐induced neuropathy [15]. Given the rarity and nonspecific early manifestations of GBS in transplant recipients, diagnostic delays are common.

We present two pediatric cases of GBS following solid organ transplantation to raise awareness of this rare but treatable complication and to emphasize the importance of early recognition in immunosuppressed patients.

2. Case 1

This is an 11‐year‐old female with acute fulminant liver failure due to Wilson's disease who underwent a reduced left lobe cadaveric liver transplant from a CMV‐positive and EBV‐positive donor. Intraoperatively she received Basiliximab 40 mg and Methylpredisolone 800 mg. Tacrolimus was started 1 day post operation, with a goal of 8–10 ng/mL. Post‐operatively, she was initiated on ganciclovir and CMV‐specific IVIG as part of CMV prophylaxis. Her immediate postoperative course was complicated by multisystem organ failure, hemorrhagic shock, disseminated intravascular coagulation (DIC), and acute kidney injury requiring continuous renal replacement therapy. She also developed an AV fistula with aneurysm at the site of an internal jugular Cordis catheter. The patient's intubation, including use of sedatives and paralytics, and post‐operative complications allowed for only a limited neurological exam.

After extubation on post‐op Day 8, she reported severe bilateral lower extremity pain and numbness and distal weakness rapidly progressing to complete inability to move her legs associated with severe distal edema. Deep venous thrombosis was ruled out on the doppler exam. Vitals were notable for tachycardia to 134, tachypnea to 33, and normal blood pressure. Neurologic examination revealed 3/5 proximal leg strength, 0/5 distal strength, diminished lower extremity reflexes with absent Achilles, and decreased pinprick in the legs with no plantar sensation to painful stimuli. Within a few days she developed ptosis, diplopia, facial weakness, and signs of bulbar involvement. Reflexes became absent in her legs. Spinal tap was not possible due to risk of bleeding as the patient was treated with clopidogrel. Multiple testing for EBV and CMV viral loads were undetectable.

Spine MRI at Day 21 demonstrated faint and questionable nerve root enhancement suggestive of inflammatory radiculopathy. Tacrolimus toxicity was considered, however levels found to be elevated at 23.4 L on Day 9 post‐op rapidly normalized within 18 hours. Workup for other infectious causes revealed adenovirus positivity. Antibody panels including anti‐MUSK, anti‐AChr, anti‐GQ1b, anti‐GM1returned negative. A week later nerve conduction studies showed no response in the bilateral superficial peroneal and sural nerves, and severely reduced motor amplitudes in both peroneal and tibial nerves. Needle EMG demonstrated spontaneous activity consistent with a severe neurogenic process. She was diagnosed with GBS with an axonal component. The patient was initiated on CMV IVIG 2 g/kg. Five days after initiation of treatment, the patient's proximal strength in lower extremities improved but the patient continued to complain of distal pain and inability to move her feet. Additional laboratory testing was negative for antibodies but positive for neurofilament light chains (3452) indicating an acute phase of AIDP. The tacrolimus level goal was maintained stable between 8 and 12 ng/mL. Over the following few months, the patient resumed independent ambulation with residual distal weakness more severe on the left with foot drop which was treated with physical therapy and ankle foot orthosis (AFO). Follow‐up spinal MRI was unremarkable. The long‐term outcome at 18 months demonstrated persistence of the left foot drop with no further improvement.

3. Case 2

This is a 9‐year‐old male with a complex medical history, including extreme prematurity at 27 weeks, chronic lung disease, and necrotizing enterocolitis requiring serial transverse enteroplasty, followed by a small bowel transplant at age 3. His post‐transplant course was complicated by post‐transplant lymphoproliferative disorder, Epstein–Barr virus (EBV) viremia, and Stage 3 graft rejection. At age 4, in the setting of significant caregiving challenges and inconsistent family support leading to medication non‐adherence and limited access to follow‐up care, he experienced a severe hypotensive episode secondary to sepsis, resulting in hypoxic brain injury with residual mild right hemiparesis and intractable epilepsy. At age 9, he presented acutely with unsteady gait and leg weakness. His vitals were notable for tachypnea to 27, but no tachycardia or hypertension. On examination, his strength was 4‐/5 in the lower extremities, with absent reflexes, inability to ambulate without assistance, severe ataxia and wide‐based gait. Sensation to light touch was intact. CSF proteins were elevated. 8 days after admission tacrolimus levels were measured as critical level of 25 ng/mL and a dose was held, then normalizing to 13.7. Spine MRI demonstrated mild to moderate contrast enhancement of the cauda equina nerve roots, predominantly anteriorly. Brain MRI revealed enhancement of cranial nerves V, VII, and VIII (see Figure 1). Based on this clinical and radiologic picture, he was diagnosed with GBS and received intravenous immunoglobulin (IVIG), 1 g/kg/day for 2 days. CMV viral load measured at this time was undetectable however EBV levels were 436 copies/mL. Two weeks later nerve conduction studies demonstrated findings consistent with severe demyelinating polyneuropathy, including prolonged distal latencies, reduced motor amplitudes, slowed conduction velocities, temporal dispersion, and absent F‐wave responses. Sensory studies showed reduced amplitudes with preserved conduction velocities. Follow up brain and spine MRI 3 months later showed no residual nerve or nerve root enhancement. Long term outcome for this patient included complete recovery to baseline mobility with residual right sided hemiparesis which was secondary to history of prior infarction.

FIGURE 1.

Case 2, Spinal and Brain MRI: T1 post‐contrast axial (left) and sagittal (center) demonstrating lumbosacral roots enhancement consistent with inflammatory radiculopathy. Cranial nerves 7 and 8 involvement with enhancement (right).

4. Discussion

Guillain‐Barré syndrome (GBS) is an acute, immune‐mediated polyradiculoneuropathy that, although well‐characterized in the general population, remains a rare and often under‐recognized complication in pediatric transplant recipients. The two cases presented, one with acute onset shortly after liver transplantation and another occurring years after small bowel transplantation, illustrate both the diagnostic complexity and clinical variability of GBS in immunosuppressed children.

GBS in healthy adult and pediatric populations is preceded and triggered by infections such as Campylobacter jejuni , Epstein–Barr virus (EBV), or cytomegalovirus (CMV) [6, 7, 15]. Post‐transplant GBS has been documented in both adult and pediatric populations. Among reported cases following solid organ transplantation, CMV infection is the most frequently implicated trigger [8]. In contrast, cases without evidence of infection suggest immunosuppressive neurotoxicity, particularly from calcineurin inhibitors such as tacrolimus and cyclosporine, and improvement has been observed after dose reduction [9, 10]. Although the development of GBS during the period of highest post‐transplant immunosuppression may appear paradoxical, the mechanisms of antirejection therapy differ from those targeted by conventional GBS treatment. Tacrolimus and cyclosporine primarily suppress T‐cell activation through calcineurin and IL‐2 inhibition, whereas GBS is mediated in large part by pathogenic antibodies, complement activation, and macrophage‐mediated injury to Schwann cells and axons [16, 17]. Accordingly, IVIG and plasma exchange act by neutralizing or removing circulating antibodies and modulating complement‐mediated inflammation rather than simply increasing T‐cell suppression [17, 18]. This distinction may explain why GBS can arise despite intensive baseline immunosuppression and why affected transplant recipients may still respond to standard GBS‐directed therapy. Consistent with this, published cases have generally been managed by maintaining baseline immunosuppression while adding IVIG or plasma exchange and treating any identified precipitating infection [10, 11, 12].

In our cases, a possible etiologic link to opportunistic viral infection was suggested by documented CMV and EBV exposure, with elevated EBV levels in Case 2. Chronic immunosuppression may predispose to viral reactivation or subclinical infection, which in turn can provoke aberrant immune responses against peripheral nerves [19]. These findings highlight the importance of routine viral surveillance in transplant recipients presenting with new‐onset weakness or sensory changes. Because a large portion of potential organ donors are CMV or EBV positive, it is standard practice to use positive donors and manage the transmission risk with preventative medication and close post‐transplant monitoring. The risk of CMV or EBV transmission is influenced by the recipient's pre‐existing serologic immunity measured by antibody levels [20, 21].

Tacrolimus‐associated neurotoxicity is a well‐recognized complication, with manifestations ranging from tremor and encephalopathy to peripheral neuropathy, typically occurring when trough levels exceed 15–20 ng/mL though can occur as therapeutic or even sub‐therapeutic levels [22]. In our first case, transient supratherapeutic tacrolimus levels (peak 23.4 ng/mL on postoperative Day 9) prompted consideration of drug toxicity. Several findings favored immune‐mediated GBS over drug toxicity, including progressive weakness despite normalized tacrolimus levels, cranial and bulbar involvement, areflexia, and axonal changes on electrophysiologic testing. Additionally, tacrolimus toxicity is not typically associated with neurofilament light chain elevation or responsiveness to IVIG therapy, both present in this patient. Elevation of serum neurofilament light chain (NfL) reflects acute axonal injury resulting from immune‐mediated peripheral nerve damage and provides supportive evidence for a new diagnosis of GBS [23]. NfL elevation is a non‐specific marker of GBS, but increased levels correlate with disease severity, axonal involvement and poorer functional outcome. This elevation often precedes electrophysiological abnormalities. NfL can be an important biomarker to support diagnosis, assess severity and potentially monitor treatments response in this complex population. Interestingly, the patient in Case 2 demonstrated an elevated neurofilament level and severe axonal involvement resulting in limited recovery, consistent with clinical expectations for this marker.

In the second case, a tacrolimus level of 25.1 ng/mL coincided with symptom onset, raising suspicion for toxicity. Yet features such as elevated cerebrospinal fluid protein, MRI findings of cauda equina and cranial nerve enhancement, and electrophysiologic evidence of demyelination supported an inflammatory rather than toxic process. The delayed improvement after drug normalization but clear response to IVIG further reinforced an immune‐mediated mechanism. Taken together, these observations suggest that while tacrolimus may exacerbate neuronal vulnerability, immune dysregulation remains the predominant driver of this disease.

The diagnosis of GBS relies on clinical and electrodiagnostic criteria established by the National Institute of Neurological Disorders and Stroke [24]. Required features include progressive, symmetric limb weakness and areflexia, while supportive findings include cranial nerve involvement, autonomic dysfunction, albuminocytologic dissociation in cerebrospinal fluid, and characteristic electrophysiologic abnormalities. In settings where lumbar puncture or MRI are delayed or contraindicated, as in our first case, nerve conduction studies and electromyography, obtained in the sub‐acute phase, can provide essential diagnostic confirmation. Both patients exhibited electrophysiologic features consistent with acute demyelinating polyneuropathy, including prolonged distal latencies, reduced motor amplitudes, temporal dispersion, and absent F‐waves. Clinicians should recognize that early electrodiagnostic studies may be normal, and treatment should not be delayed when the clinical suspicion for GBS is high. Dysautonomia with cardiovascular instability including tachy‐ bradycardia, arrhythmia, hyper‐ or hypo‐tension, and diaphoresis is frequently associated with GBS. Although no clear dysautonomia was identified in our patients, the extremely lower extremity edema in Case 1 could have been secondary to involvement of perivascular autonomic fibers [25].

The timing and evolution of these cases emphasize the need for sustained vigilance across the transplant continuum. Although GBS typically presents acutely or sub‐acutely, it may also arise years after transplantation, particularly in the setting of chronic immune dysregulation or medication nonadherence. Prognosis remains variable and may depend on the extent of axonal injury, response to immunotherapy, and preexisting neurologic comorbidities.

Finally, the first case underscores how diagnosis may be delayed in critically ill patients due to overlapping etiologies, such as medication effects, metabolic derangements, or sedation, and limited access to diagnostic modalities. In such scenarios, a multidisciplinary approach integrating neurology, infectious disease, and transplant teams is essential to expedite recognition and initiate timely immunotherapy. Transplant and medical teams caring for post‐transplant patients should consider GBS in the differential diagnosis. In critically ill, intubated, or sedated patients, limited spontaneous movement may reflect multiple factors and should not preclude consideration of GBS. GBS can occur in these settings, and maintaining awareness is key to timely identification and treatment.

5. Conclusion

In transplant recipients with unexplained neurologic decline, clinicians should consider the possibility of immune‐mediated neuropathy even when alternative explanations, such as tacrolimus toxicity or critical illness, are present. When feasible, timely electrodiagnostic testing, CSF analysis, brain and spine MRI with and without contrast and early initiation of immunotherapy may help improve outcomes. Attention to viral surveillance and careful monitoring of immunosuppressive therapy may also provide helpful diagnostic context.

In summary, these cases highlight that GBS, though rare, should be included in the differential diagnosis of new‐onset weakness in pediatric transplant recipients. Early recognition and treatment are crucial to prevent long‐term morbidity. Awareness of its varied presentations, particularly in the context of immunosuppressive therapy and viral reactivation, can facilitate prompt diagnosis and optimize neurologic outcomes in this vulnerable population.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.