What are the differential diagnoses for bulbar palsy?

Differential Diagnosis of Bulbar Palsy

The differential diagnosis of bulbar palsy requires systematic categorization into peripheral nervous system, central nervous system, neuromuscular junction, muscle, and metabolic causes, with urgent evaluation for red flags that indicate life-threatening conditions requiring immediate intervention. 1

Peripheral Nervous System Causes

• Guillain-Barré Syndrome variants are critical peripheral causes, particularly the pharyngeal-cervical-brachial variant which presents with weakness of pharyngeal, cervical, and brachial muscles without lower limb involvement 1
• Classic GBS features include progressive bilateral weakness developing over days to 4 weeks with absent or decreased reflexes, elevated CSF protein with normal cell count, and electrodiagnostic evidence of motor or sensorimotor neuropathy 1
• Miller Fisher syndrome presents with the triad of ophthalmoplegia, ataxia, and areflexia, with 15% overlapping with classical sensorimotor GBS and potential bulbar involvement 1
• Compression or infiltration of lower cranial nerves from malignancy must be excluded, as structural lesions of the hypoglossal nerve can mimic bulbar onset amyotrophic lateral sclerosis 1, 2

Central Nervous System Causes

• Brainstem stroke should be considered when bulbar symptoms are accompanied by crossed sensory/motor deficits or cranial nerve findings 1
• Pseudobulbar palsy from bilateral corticobulbar tract lesions (such as consecutive lacunar strokes) can present with dramatic bulbar symptoms including dysphagia, anarthria, and glossplegia despite relatively small lesions 3
• Multiple sclerosis with brainstem involvement presents with multifocal symptoms evolving over hours to days, with MRI showing periventricular white matter lesions that are sharply demarcated and round or flame-shaped 1
• Brainstem inflammation from sarcoidosis, Sjögren syndrome, neuromyelitis optica, or myelin oligodendrocyte glycoprotein antibody-associated disorder can cause bulbar symptoms 1
• Acute transverse myelitis affecting the brainstem can present with bulbar dysfunction 1

Neuromuscular Junction Disorders

• Myasthenia gravis presents with fatigable bulbar weakness, fluctuating dysarthria, and dysphagia that worsens with repetitive use 1
• Lambert-Eaton myasthenic syndrome can present with bulbar symptoms alongside autonomic dysfunction 1
• Botulism causes descending paralysis with prominent early bulbar involvement and autonomic dysfunction, requiring urgent evaluation when rapid progression occurs 1

Muscle Disorders

• Inflammatory myositis affecting bulbar muscles can cause dysphagia and dysarthria 1
• Oculopharyngeal muscular dystrophy presents with progressive dysphagia and ptosis, typically after age 50 1
• Mitochondrial diseases, particularly chronic progressive external ophthalmoplegia syndromes, can have bulbar involvement 1

Metabolic and Nutritional Causes

• Vitamin B12 deficiency causes subacute combined degeneration of the spinal cord with potential bulbar involvement, presenting with both central and peripheral manifestations 1
• Wernicke encephalopathy from vitamin B1 deficiency can affect brainstem structures 1
• Electrolyte disturbances including hypokalaemia, hypomagnesaemia, and hypophosphataemia can trigger bulbar symptoms through altered nerve excitability 1

Motor Neuron Disease Considerations

• Progressive bulbar palsy is a classic phenotype of bulbar onset ALS with rapid progression and worse prognosis, where bulbar dysfunction contributes to respiratory complications including aspiration pneumonia, upper airway obstruction, and inadequate cough clearance 4, 5
• Isolated bulbar palsy (IBP) is an under-recognized variant characterized by symptoms confined to the bulbar region for extended periods (>20 months before limb involvement), female predominance, pure upper motor neuron bulbar signs, and relatively benign prognosis with median survival of 64 months versus 26 months for typical bulbar onset ALS 5, 6

Critical Red Flags Requiring Urgent Evaluation

• Fever at onset suggests infection or inflammatory process requiring immediate CSF analysis 1
• Rapid progression with respiratory failure within 24 hours suggests botulism, myasthenic crisis, or brainstem stroke 1
• Bladder or bowel dysfunction at onset suggests cauda equina syndrome or spinal cord compression rather than isolated bulbar pathology 1
• Altered consciousness suggests CNS pathology beyond typical peripheral neuropathy 1

Diagnostic Approach Algorithm

Step 1: Document temporal pattern - Determine if presentation is hyperacute, acute (days to 4 weeks), subacute, or chronic, as this narrows the differential significantly 1

Step 2: Initial laboratory assessment - Obtain complete blood count, comprehensive metabolic panel, and vitamin B12 level to exclude metabolic causes 1

Step 3: Cerebrospinal fluid analysis - Perform lumbar puncture when infection, inflammation, or GBS is suspected; elevated protein with normal cell count is classic for GBS 1

Step 4: Neuroimaging - Brain and spine MRI with gadolinium is essential to exclude brainstem stroke, compression, inflammation, or demyelination 1

Step 5: Swallowing assessment - Perform swallow screening and videofluoroscopy or fiberoptic endoscopic evaluation of swallowing for patients with positive screening or high aspiration risk, as abnormal respiratory patterns during swallow (inspiration after swallow, prolonged swallow apnoea) are common in bulbar dysfunction 1, 4

Common Pitfalls to Avoid

• Do not rely solely on forced vital capacity in patients with bulbofacial weakness, as volitional respiratory function tests can be inaccurate in this population 4
• Do not assume brainstem localization based solely on bulbar symptoms, as pseudobulbar palsy from bilateral supratentorial lesions can mimic brainstem pathology with dramatic clinical presentations 3
• Do not diagnose bulbar onset ALS without excluding structural lesions of cranial nerves, particularly hypoglossal nerve pathology, as misdiagnosis has significant implications on quality of life and future planning 2