How to diagnose Immune Checkpoint Inhibitor (ICPi)-mediated Guillain-Barré Syndrome (GBS)?

Diagnosing ICPi-Mediated Guillain-Barré Syndrome

Suspect ICPi-mediated GBS in any patient on checkpoint inhibitor therapy who develops subacute progressive limb weakness, sensory loss, and areflexia, and immediately initiate the diagnostic workup below, as all grades warrant urgent evaluation given the potential for rapid progression to respiratory compromise. 1, 2

Clinical Presentation to Recognize

• Progressive, typically symmetrical muscle weakness with absent or reduced deep tendon reflexes 1
• Sensory symptoms or neuropathic pain often starting in the lower back and thighs before ascending 1
• Ascending weakness pattern (though not always) involving extremities, facial muscles, respiratory muscles, and bulbar/oculomotor nerves 1
• Autonomic dysregulation may be present 1
• Critical warning signs: ANY dysphagia, facial weakness, respiratory muscle weakness, or rapidly progressive symptoms require immediate escalation 1

Essential Diagnostic Workup

Immediate Neurology Consultation

• Obtain neurology consultation immediately for all suspected cases 1

Spinal Imaging

• MRI of spine with and without contrast to rule out compressive lesions and evaluate for nerve root enhancement/thickening 1

Lumbar Puncture

• CSF analysis typically shows elevated protein and often elevated WBCs (albuminocytologic dissociation) 1
• Important caveat: Unlike classic idiopathic GBS, ICPi-related GBS commonly shows elevated WBCs in CSF 1
• Always send cytology with any CSF sample from a patient with cancer to rule out leptomeningeal disease 1
• Check: cell count and differential, protein, glucose, gram stain, bacterial/viral cultures 1

Electrodiagnostic Studies

• Nerve conduction studies (NCS) and electromyography (EMG) to evaluate for polyneuropathy and confirm demyelinating pattern 1, 3
• Findings typically show: acquired demyelinating polyneuropathy pattern 3

Serologic Testing

• Serum antiganglioside antibody tests for GBS and its subtypes 1
• Specifically test for anti-GQ1b if Miller Fisher variant suspected (associated with ataxia and ophthalmoplegia) 1

Pulmonary Function Assessment

• Baseline pulmonary function testing including negative inspiratory force (NIF) and vital capacity 1, 4
• Establish monitoring protocol as respiratory compromise can develop rapidly 1, 4

Additional Monitoring Requirements

Cardiac Evaluation

• ECG and transthoracic echocardiogram if there is respiratory insufficiency or elevated CPK/troponin to evaluate for concomitant myocarditis 1
• Monitor for arrhythmias and blood pressure fluctuations due to autonomic dysfunction 4

Exclude Alternative Diagnoses

• Screen for reversible causes: HbA1c, vitamin B12, folate, TSH, vitamin B6, HIV 1
• Consider: serum protein electrophoresis, immunofixation, autoimmune screening (ANA, ESR, CRP, ANCA) 1
• MRI brain if cranial nerve involvement to rule out CNS disease 1

Critical Pitfalls to Avoid

• Do not wait for classic albuminocytologic dissociation without WBC elevation - ICPi-related GBS often presents with elevated CSF WBCs unlike idiopathic GBS 1
• Do not delay workup based on symptom severity - there is no Grade 1 toxicity for GBS; all presentations warrant immediate evaluation 1
• Do not miss concurrent myocarditis - check cardiac biomarkers and perform cardiac evaluation if any respiratory symptoms or elevated muscle enzymes 1
• Do not overlook autonomic dysfunction - monitor orthostatic vital signs and cardiac rhythm continuously 1, 4
• Always send CSF cytology in cancer patients to exclude leptomeningeal metastases as an alternative diagnosis 1

Severity Assessment for Management Planning

Once diagnosed, grade severity to guide treatment intensity:

• Grade 2: Moderate symptoms with some ADL interference but no severe weakness 1
• Grade 3-4: Severe disease with limiting self-care, weakness limiting walking, ANY dysphagia/facial/respiratory weakness, or rapidly progressive symptoms 1

All grades require ICPi discontinuation and admission to a unit with rapid ICU transfer capability given the unpredictable potential for respiratory decompensation 1.