What are the differential diagnoses for bulbar palsy?

Differential Diagnosis of Bulbar Palsy

The differential diagnosis of bulbar palsy is broad and must systematically distinguish between lower motor neuron (true bulbar palsy) and upper motor neuron (pseudobulbar palsy) causes, with critical attention to CNS inflammation, peripheral neuropathies, neuromuscular junction disorders, and structural lesions that can mimic bulbar-onset motor neuron disease.

Peripheral Nervous System Causes (True Bulbar Palsy)

Guillain-Barré Syndrome and Variants

• Pharyngeal-cervical-brachial variant (<5% of GBS cases) presents with weakness of pharyngeal, cervical and brachial muscles without lower limb weakness, representing a critical bulbar-predominant presentation 1
• Classic GBS features include progressive bilateral weakness over days to 4 weeks with absent or decreased reflexes, elevated CSF protein (though normal protein does not exclude diagnosis), and electrodiagnostic evidence of motor or sensorimotor neuropathy 1
• Bilateral facial palsy variant (<5% of cases) presents with bilateral facial weakness, paresthesias and reduced reflexes, which can accompany bulbar symptoms 1
• Miller Fisher syndrome (5-25% of GBS cases) presents with ophthalmoplegia, ataxia and areflexia, with 15% overlapping with classical sensorimotor GBS and potential bulbar involvement 1
• Bickerstaff brainstem encephalitis (<5% of cases) presents with ophthalmoplegia, ataxia, areflexia, pyramidal tract signs and impaired consciousness, often overlapping with sensorimotor GBS 1

Motor Neuron Disease

• Bulbar-onset ALS presents with insidious progression of dysphagia, dysarthria, and dyspnea, with typical progression to limb involvement within 20 months distinguishing it from isolated bulbar palsy 2
• Isolated bulbar palsy (IBP) is characterized by symptoms confined to the bulbar region for >20 months before significant limb involvement, female predominance, pure upper motor neuron bulbar signs, and median survival of 64 months versus 26 months for typical bulbar-onset ALS 2
• Progressive bulbar palsy represents classic bulbar-onset ALS with more rapid progression and worse prognosis 3

Structural Nerve Lesions

• Hypoglossal nerve lesions from structural pathology can mimic bulbar-onset ALS and must be excluded before diagnosing motor neuron disease 4
• Compression or infiltration of lower cranial nerves (IX, X, XI, XII) from malignancy, particularly leptomeningeal metastases or neurolymphomatosis, should be considered 1

Central Nervous System Causes (Pseudobulbar Palsy)

Vascular Causes

• Bilateral lacunar strokes affecting both corticobulbar tracts can present with sudden onset dysphagia, anarthria, and glossoplegia mimicking brainstem lesions, with clinically dramatic presentations despite small lesion size 5
• Brainstem stroke should be considered when bulbar symptoms are accompanied by crossed sensory/motor deficits or cranial nerve findings 6
• Cerebral venous thrombosis involving the sagittal sinus can cause bilateral motor signs including bulbar dysfunction 6

Inflammatory and Demyelinating Conditions

• Brainstem inflammation from sarcoidosis, Sjögren syndrome, neuromyelitis optica, or myelin oligodendrocyte glycoprotein antibody-associated disorder can cause bulbar symptoms 1
• 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 may enhance with gadolinium 6
• Acute transverse myelitis affecting the brainstem can present with bulbar dysfunction 1

Infectious Causes

• Lyme disease encephalomyelitis is rare but presents with multifocal CNS involvement, CSF lymphocytic pleocytosis, and positive two-tier serology with intrathecal antibody production 6
• Brainstem infection or abscess should be considered, particularly with fever at onset 1

Structural CNS Lesions

• Compression of the brainstem from tumor, abscess, or posterior fossa mass lesions can cause progressive bulbar symptoms 1
• Malignancy including leptomeningeal metastases or neurolymphomatosis affecting the brainstem or lower cranial nerves 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, 6
• 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, 6

Neuromuscular Junction Disorders

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

Muscle Disorders

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

Critical Red Flags Requiring Urgent Evaluation

• Fever at onset suggests infection or inflammatory process requiring immediate CSF analysis 1
• Bladder or bowel dysfunction at onset suggests cauda equina syndrome or spinal cord compression rather than isolated bulbar pathology 1
• Altered consciousness (except in Bickerstaff brainstem encephalitis) suggests CNS pathology beyond typical peripheral neuropathy 1, 6
• Rapid progression with respiratory failure within 24 hours suggests botulism, myasthenic crisis, or brainstem stroke 1
• Marked persistent asymmetry of bulbar weakness casts doubt on GBS and suggests structural lesion 1

Diagnostic Approach Algorithm

Initial Clinical Assessment

• Document temporal pattern: hyperacute (<24h suggests vascular), acute (days to 4 weeks suggests GBS), subacute (weeks to months suggests inflammatory or degenerative), or chronic (>4 weeks suggests motor neuron disease) 1, 6
• Distinguish true bulbar palsy (lower motor neuron: fasciculations, atrophy, absent gag reflex, flaccid tongue) from pseudobulbar palsy (upper motor neuron: spastic tongue, hyperactive gag, emotional lability) 5
• Assess for cranial nerve involvement pattern: bilateral facial palsy strongly supports GBS, while isolated hypoglossal palsy suggests structural lesion 1, 4

Laboratory Investigations

• Complete blood count, comprehensive metabolic panel including electrolytes, glucose, kidney and liver function to exclude metabolic causes 1, 6
• Vitamin B12 level and methylmalonic acid if deficiency suspected 1, 6
• Thyroid function tests as hyperthyroidism can precipitate paroxysmal symptoms 6
• Serum ferritin if concurrent restless legs symptoms present 6

Cerebrospinal Fluid Analysis

• Elevated protein with normal cell count (<10 cells/μL) is classic for GBS, though normal protein does not exclude early GBS 1
• >50 mononuclear or polymorphonuclear cells/μL casts doubt on GBS diagnosis and suggests CNS infection or inflammation 1
• Lyme serology with intrathecal antibody production if endemic area and subacute presentation 6

Neurophysiological Studies

• Nerve conduction studies and EMG differentiate demyelinating (AIDP) from axonal (AMAN/AMSAN) GBS subtypes, though one-third of patients are "equivocal" or "inexcitable" initially 1, 6
• Repetitive nerve stimulation and single-fiber EMG for suspected myasthenia gravis
• Repeat electrodiagnostic studies 3-8 weeks after onset may aid classification if initially equivocal 1

Neuroimaging

• Brain and spine MRI with gadolinium is essential to exclude brainstem stroke, compression, inflammation, or demyelination 6, 5
• MRI showing bilateral internal capsule lacunes with bulbar symptoms confirms pseudobulbar palsy 5
• Periventricular white matter lesions that are sharply demarcated and spare U-fibers suggest multiple sclerosis 6

Swallowing Assessment

• All patients require swallow screening before oral intake to prevent aspiration 7
• Videofluoroscopy (VFSS) or fiberoptic endoscopic evaluation of swallowing (FEES) for patients with positive screening or high aspiration risk 7

Common Pitfalls to Avoid

• Do not diagnose bulbar-onset ALS without excluding structural hypoglossal nerve lesions with neuroimaging, as these are treatable mimics 4
• Do not assume brainstem localization based solely on bulbar symptoms, as bilateral supranuclear lesions (pseudobulbar palsy) can present identically and require different management 5
• Do not rule out GBS based on normal CSF protein or electrophysiology early in disease course, as these findings may normalize initially and abnormalities develop over days to weeks 1
• Do not overlook respiratory monitoring in all bulbar palsy patients, as respiratory failure can occur without dyspnea symptoms, requiring serial vital capacity, maximum inspiratory pressure, and maximum expiratory pressure measurements 7, 8
• Do not delay nutritional assessment and intervention, as chronic malnutrition from bulbar dysfunction significantly impacts respiratory muscle function and survival 7, 8