What are the causes of intentional tremor in a patient with a history of neurological disorders such as multiple sclerosis, Parkinson's disease, or cerebellar ataxia?

Causes of Intentional Tremor

Intentional tremor (also called intention tremor) is primarily caused by lesions affecting the cerebellum and its connected pathways, with multiple sclerosis, cerebellar stroke, and hereditary cerebellar ataxias being the most common etiologies. 1

Primary Cerebellar Pathology

Demyelinating Disease

• Multiple sclerosis is a major cause of intention tremor due to demyelinating plaques affecting cerebellar pathways and connections 2, 3
• Demyelinating lesions in the brainstem and cerebellar peduncles disrupt coordination pathways, producing the characteristic tremor that worsens with goal-directed movement 4
• Isoniazid may control cerebellar tremor associated with multiple sclerosis, though evidence is limited 2

Vascular Causes

• Posterior circulation stroke affecting the cerebellum produces acute-onset intention tremor and ataxia 5
• Vertebrobasilar insufficiency can present with episodic or progressive ataxia and tremor 5
• Spinal dural arteriovenous fistulae can cause cord edema resulting in ataxia and tremor 4

Hereditary Cerebellar Degenerations

• Spinocerebellar ataxias (SCAs) represent genetically heterogeneous autosomal dominant disorders that commonly produce intention tremor as cerebellar degeneration progresses 5
• Friedreich ataxia, the major autosomal recessive cerebellar ataxia, presents with progressive intention tremor and associated spinal cord involvement 5
• Ataxia-telangiectasia presents with cerebellar ataxia and characteristic telangiectasias 5
• Fragile X-associated tremor/ataxia syndrome should be considered in the differential diagnosis of genetic tremor syndromes 3

Structural Lesions

• Cerebellar tumors and brain stem gliomas are common causes of chronic progressive ataxia and intention tremor that must be excluded early 5
• Space-occupying lesions directly compress or infiltrate cerebellar tissue and pathways 5

Secondary Causes

Inflammatory and Autoimmune

• Acute cerebellitis presents with truncal ataxia, dysmetria, and intention tremor, with severe cases developing altered consciousness 5
• Postinfectious cerebellar ataxia accounts for approximately 50% of pediatric acute ataxia presentations 5
• Neurosarcoidosis can affect the cerebellum and produce intention tremor 4
• Autoimmune cerebellitis or cerebellar degeneration should be considered with prominent cerebellar symptoms 6

Metabolic and Toxic

• Wilson's disease can present with tremor, dystonia, and cerebellar features, though rare in older adults 7
• Nutritional deficiencies including B12 deficiency and copper deficiency can cause cerebellar dysfunction 4
• Alcohol withdrawal can produce cerebellar tremor 2

Paraneoplastic Syndromes

• Paraneoplastic cerebellar degeneration produces subacute progressive intention tremor and ataxia 4
• Testing for paraneoplastic antibodies is essential when cerebellar symptoms develop rapidly in adults 5

Neurodegenerative Disorders

• Holmes tremor (previously called rubral tremor) results from lesions affecting the cerebellothalamic pathways and presents with combined rest, postural, and intention components 3
• Essential tremor, while primarily a postural/action tremor, often manifests intention tremor and mild gait ataxia due to cerebellar dysfunction 8
• Multiple system atrophy (MSA-C subtype) presents with ataxia and cerebellar symptoms predominating, which produces intention tremor 7

Diagnostic Algorithm

Initial Clinical Assessment

• Characterize the tremor precisely: intention tremor worsens during goal-directed movements (finger-to-nose, heel-to-shin testing) and increases in amplitude as the target is approached 1, 9
• Assess for associated cerebellar signs: dysmetria, dysdiadochokinesia, dysarthria, nystagmus, and truncal ataxia 5
• Determine time course: acute (stroke, cerebellitis), subacute (inflammatory, paraneoplastic), or chronic progressive (hereditary, degenerative) 5

Imaging

• MRI brain without IV contrast is the optimal initial imaging modality to evaluate cerebellar pathology, detecting structural lesions, demyelinating plaques, atrophy, and signal abnormalities 4, 5
• MRI of the complete spine should be obtained when spinocerebellar ataxias are suspected or when spinal cord signs are present 5
• For acute presentations, prioritize exclusion of stroke, hemorrhage, and mass lesions 5

Laboratory Evaluation

• Serum ceruloplasmin and 24-hour urinary copper for Wilson's disease; look for Kayser-Fleischer rings on slit-lamp examination 7
• Vitamin B12, copper, and vitamin E levels for nutritional deficiencies 4, 6
• Thyroid function tests to exclude metabolic causes 7
• Paraneoplastic antibody panel if subacute progressive course 5
• Genetic testing for spinocerebellar ataxias if family history or progressive course without other explanation 6

Critical Pitfalls to Avoid

• Do not assume all intention tremor is benign essential tremor—always exclude structural lesions, multiple sclerosis, and paraneoplastic syndromes first, as these directly impact mortality and are potentially treatable 5, 3
• Do not rely solely on initial imaging in suspected hereditary ataxias—early scans may appear normal or subtly abnormal, with progressive cerebellar atrophy becoming apparent only on follow-up imaging 5
• Cerebellar ataxia shows unsteadiness that does not significantly worsen with eye closure, distinguishing it from sensory ataxia 5
• At advanced age, consider that multiple pathologies may coexist (vascular changes plus neurodegenerative disease) 7