What is the workup for ataxia and dystonia?

Workup for Ataxia and Dystonia

Begin with a detailed neurological history and examination to localize the lesion, then proceed with brain MRI as the primary imaging modality, followed by targeted laboratory testing and genetic evaluation based on clinical presentation and imaging findings. 1

Initial Clinical Assessment

History and Examination Priorities

Determine the time course of symptom onset:

• Acute onset (hours to days): Consider stroke, cerebellitis, toxins, trauma, or Miller-Fisher syndrome 1
• Subacute/chronic progressive: Consider genetic disorders, metabolic conditions, or neurodegenerative processes 1, 2
• Episodic/intermittent: Consider migraine-related ataxia, metabolic disorders, or benign positional vertigo 1

Identify localizing neurological signs:

• Truncal ataxia and titubation: Midline cerebellar pathology 1
• Limb ataxia with hyperreflexia, spasticity, sensory loss: Spinal cord involvement 1
• Ataxia worsening with eye closure (positive Romberg): Proprioceptive/sensory ataxia from dorsal column or peripheral nerve dysfunction 1, 3
• Nausea, vomiting, vertigo: Vestibulo-cerebellar system involvement 1
• Dystonia with ataxia: Consider genetic dystonia-ataxia syndromes, basal ganglia involvement, or specific conditions like ataxia-telangiectasia 1, 2, 4

Key red flags requiring urgent imaging:

• Extracerebellar symptoms (somnolence, encephalopathy, focal weakness, cranial nerve deficits) 1
• Age >3 years with symptoms >3 days duration 1
• Recent head trauma 1
• Suspected acute stroke 1

Imaging Strategy

Primary Imaging: Brain MRI

Brain MRI with and without contrast is the preferred initial imaging modality for ataxia and dystonia workup. 1

MRI detects significantly more abnormalities than CT:

• MRI identifies abnormalities in 14% of children with acute ataxia versus 7% on CT 1
• MRI sensitivity for clinically significant findings is 5% versus 2.5% for CT 1
• MRI provides superior visualization of cerebellar structures, brainstem, basal ganglia, and white matter 1

Specific MRI sequences and findings to evaluate:

• Cerebellar atrophy or structural abnormalities 1
• Basal ganglia lesions (particularly putamen in dystonia-ataxia syndromes) 5, 4
• Brainstem abnormalities (pons, thalamus) 1, 4
• White matter changes suggesting demyelination or metabolic disorders 1
• Posterior fossa masses or hydrocephalus 1

Spinal Imaging When Indicated

MRI of cervical and thoracic spine is recommended when:

• Clinical signs suggest spinal cord involvement (hyperreflexia, spasticity, sensory level) 1, 3
• Proprioceptive ataxia is suspected (positive Romberg, sensory loss, hyporeflexia) 1, 3
• Myelopathy is in the differential diagnosis 1

CT Head: Limited Role

CT head is reserved for specific acute scenarios:

• Suspected acute intracranial hemorrhage when MRI unavailable 1
• Acute trauma setting for rapid assessment 1
• Evaluation of hydrocephalus or calcifications 1
• When MRI is contraindicated or unavailable 1

Important caveat: In young children with acute cerebellar ataxia following recent viral illness, without extracerebellar signs and negative toxicology, watchful waiting may be appropriate with imaging reserved for clinical deterioration 1

Laboratory Evaluation

Initial Laboratory Testing

Order the following based on clinical presentation:

• Toxicology screen: Essential in acute ataxia, especially in children and young adults 1
• Metabolic panel: Glucose, electrolytes, liver function, renal function 1
• Thyroid function tests: Hypothyroidism can cause cerebellar dysfunction 1
• Vitamin levels: B12, thiamine, vitamin E (especially with chronic ataxia or nutritional concerns) 1
• Infectious workup: If cerebellitis suspected (CSF analysis, viral serologies) 1

Specialized Testing for Dystonia-Ataxia

When dystonia accompanies ataxia, consider:

• Ceruloplasmin and 24-hour urine copper: Wilson disease screening 2
• Acanthocytes on blood smear: Neuroacanthocytosis syndromes 2
• Lactate and pyruvate: Mitochondrial disorders 2, 4
• Very long chain fatty acids: Peroxisomal disorders 2
• Anti-GQ1b antibody: Miller-Fisher syndrome 1

Genetic Testing Strategy

When to Pursue Genetic Testing

Genetic evaluation is indicated for:

• Progressive ataxia with family history 1, 2
• Early-onset ataxia (<25 years) with dystonia 2, 4
• Chronic progressive ataxia without identified acquired cause 1, 2
• Ataxia with additional features suggesting genetic syndrome (telangiectasias, retinopathy, skeletal abnormalities) 1, 2

Genetic testing approach:

• Whole-exome sequencing is increasingly the preferred initial approach for complex phenotypes combining ataxia and dystonia 6, 4
• Targeted gene panels: Consider comprehensive movement disorder panels rather than single-disease panels, as many genes can cause both ataxia and dystonia 2, 4
• Specific single-gene testing when clinical phenotype strongly suggests particular diagnosis (e.g., Friedreich ataxia, spinocerebellar ataxias) 1, 2

Pathophysiological insight: Genetic dystonia-ataxia syndromes often involve shared pathways affecting cellular energy metabolism, organelle organization, and signal transduction, particularly in basal ganglia, cerebellum, and brainstem 4

Algorithmic Approach by Clinical Scenario

Acute Ataxia (<72 hours)

1. Immediate assessment: Exclude stroke, hemorrhage, trauma 1
2. Imaging: Brain MRI preferred; CT if MRI unavailable or contraindicated 1
3. Laboratory: Toxicology screen, metabolic panel, infectious workup if febrile 1
4. Special consideration: In children with isolated acute cerebellar ataxia post-viral illness, imaging may be deferred with close observation 1

Chronic Progressive Ataxia with Dystonia

1. Imaging: Brain MRI with attention to cerebellum, basal ganglia, brainstem 1, 4
2. Laboratory: Comprehensive metabolic workup including Wilson disease screening, vitamin levels 2
3. Genetic testing: Whole-exome sequencing or comprehensive movement disorder panel 2, 6, 4
4. Functional imaging: Consider dopamine receptor imaging if basal ganglia involvement suspected 5

Proprioceptive Ataxia (Positive Romberg)

1. Spinal imaging: MRI cervical and thoracic spine to evaluate dorsal columns 1, 3
2. Nerve conduction studies: Assess peripheral nerve function 1, 3
3. Laboratory: B12, vitamin E, copper levels; consider paraneoplastic antibodies 1, 3

Common Pitfalls to Avoid

Do not rely solely on CT in non-acute settings - MRI detects twice as many clinically significant abnormalities 1

Do not order single-disease genetic panels for dystonia-ataxia - use comprehensive movement disorder panels or whole-exome sequencing given overlapping pathophysiology 2, 4

Do not assume all ataxia is cerebellar - systematically evaluate for spinal cord, peripheral nerve, and vestibular causes through examination and appropriate imaging 1, 3

Do not overlook treatable causes - Wilson disease, vitamin deficiencies, toxins, and infections require specific testing and have treatment implications 1, 2