What are the possible causes of unilateral base of tongue droopiness in a patient, excluding stroke?

Unilateral Base of Tongue Droopiness: Non-Stroke Etiologies

The most critical non-stroke cause of unilateral tongue droopiness is hypoglossal nerve (CN XII) palsy, most commonly due to neoplasm involving the hypoglossal canal or malignant tumors along the carotid space and sublingual space, requiring urgent contrast-enhanced MRI of the brain and neck to evaluate the entire course of CN XII from brainstem to tongue musculature. 1

Primary Diagnostic Considerations

Neoplastic Causes (Most Common)

• Malignant tumors are the leading cause of isolated hypoglossal nerve palsy, particularly those involving the hypoglossal canal at the skull base or along the extracranial course of CN XII in the carotid space and sublingual space 1
• Nerve sheath tumors (schwannomas) can directly compress CN XII along its course 1
• Metastatic disease to the skull base or posterior fossa can present with isolated tongue weakness 2

Vascular Causes

• Internal carotid artery dissection can result in isolated acute CN XII palsy or multiple cranial nerve palsies involving CN IX through CN XII 1
• This represents a critical diagnosis requiring urgent vascular imaging with CTA or MRA 2

Inflammatory and Infectious Processes

• Neuritis affecting the hypoglossal nerve can cause unilateral tongue weakness with characteristic enhancement on MRI 1
• Infectious etiologies including viral, bacterial, Lyme disease, tuberculosis, syphilis, and fungal infections can affect cranial nerves 1
• Sarcoidosis can cause cranial neuropathies including CN XII involvement 1

Demyelinating Disease

• Multiple sclerosis can present with isolated cranial nerve palsies including hypoglossal nerve involvement 1
• MRI typically shows characteristic white matter lesions in addition to brainstem involvement 1

Trauma

• Direct injury to the hypoglossal nerve at any point along its course from brainstem through the hypoglossal canal to the tongue musculature 1
• Temporal bone fractures or skull base trauma 1

Neuromuscular Junction Disorders

• Myasthenia gravis can present with unilateral bulbar weakness including tongue involvement, though this is an uncommon initial presentation 3, 4, 5
• Cranial nerve IX and X weakness (dysphagia, dysphonia) may accompany or precede tongue weakness in myasthenia gravis 5
• This diagnosis is particularly important as it is treatable and can be life-threatening if missed 3, 4

Critical Diagnostic Algorithm

Immediate Imaging

Contrast-enhanced MRI of the brain and neck is the essential first-line study to directly image the brainstem, intracranial and skull base segments of the hypoglossal nerve, and assess for lesions along the extracranial segments 1

Complementary Imaging

• High-resolution CT of the skull base with contrast provides complementary information characterizing osseous integrity of the hypoglossal canal 1
• CTA or MRA of the head and neck should be obtained if vascular dissection or compression is suspected 2

Laboratory Evaluation

• Acetylcholine receptor antibodies should be sent if myasthenia gravis is suspected, particularly if symptoms fluctuate or involve other cranial nerves 3, 4
• ESR and CRP if giant cell arteritis is considered (age >50 with temporal symptoms) 6
• Lyme serology only in endemic areas with appropriate exposure history 6

Key Clinical Features to Assess

Direction of Tongue Deviation

• In lower motor neuron (peripheral) CN XII lesions, the tongue deviates toward the side of weakness upon protrusion 1
• This is accompanied by ipsilateral tongue atrophy and fasciculations over time 1

Associated Neurologic Deficits

• Nuclear (brainstem) lesions are usually accompanied by additional neurologic deficits indicating brainstem involvement 1
• Multiple cranial nerve involvement (CN IX, X, XI with XII) suggests jugular foramen or brainstem pathology 1
• Contralateral tongue deviation with ipsilateral facial symptoms suggests upper motor neuron pathology requiring urgent neuroimaging 2

Temporal Pattern

• Acute onset suggests vascular etiology (dissection) or trauma 1
• Progressive symptoms suggest neoplasm 1
• Fluctuating weakness suggests myasthenia gravis 3, 4, 5

Common Diagnostic Pitfalls

Do Not Assume Stroke Without Imaging

• While brainstem infarct can cause hypoglossal nerve palsy, most isolated CN XII palsies are due to neoplasm, not stroke 1
• Routine head CT is inadequate and should not be used for initial evaluation of isolated CN XII palsy 1

Do Not Miss Myasthenia Gravis

• Myasthenia gravis can present with unilateral cranial nerve symptoms without the hallmark fluctuating weakness, particularly in acute presentations 3, 4
• This diagnosis is critical as it is treatable and can progress to respiratory failure if missed 5
• Consider acetylcholine receptor antibody testing even with persistent unilateral symptoms 3, 4

Do Not Overlook Carotid Dissection

• Internal carotid artery dissection can present as isolated CN XII palsy without other obvious vascular symptoms 1
• This requires urgent vascular imaging with CTA or MRA 2

Recognize Red Flags for Urgent Evaluation

• Progressive symptoms beyond 2-4 months warrant imaging even if initially thought benign 6
• Additional cranial nerve involvement (dysphagia, dysphonia, facial weakness) suggests more extensive pathology 1, 5
• Age over 50 with new cranial nerve symptoms requires consideration of giant cell arteritis or malignancy 6

MRI Findings to Anticipate

• Denervation signal alterations in the tongue musculature vary with duration of palsy 1
• Direct visualization of nerve enhancement suggests neuritis or tumor 1
• Atrophy of tongue musculature on the affected side develops over time 1
• Lesions along the entire course from dorsal medulla through hypoglossal canal to carotid space must be evaluated 1