What is the differential diagnosis for a patient presenting with movement disorders, including potential underlying causes and appropriate diagnostic and treatment approaches?

Movement Disorder Differential Diagnosis

Primary Classification Framework

Movement disorders are fundamentally divided into two categories: hypokinetic (reduced movement) and hyperkinetic (excessive movement), with the dominant phenomenology guiding your entire diagnostic approach. 1, 2

Hypokinetic Disorders (Parkinsonian Syndromes)

Cardinal features include bradykinesia (essential for diagnosis) plus at least one of: resting tremor, rigidity, or postural instability. 3

Idiopathic Parkinson's Disease

• Asymmetric resting tremor, rigidity, and bradykinesia appearing at age 60-70 years 3, 4
• Symptoms manifest after 40-50% of substantia nigra dopaminergic neurons are lost 3, 4
• MRI brain without contrast is the initial imaging study, though often normal early in disease 3
• I-123 ioflupane SPECT/CT (DaTscan) differentiates PD from essential tremor or drug-induced tremor; a normal scan excludes parkinsonian syndromes 3
• Histopathology shows intracellular alpha-synuclein inclusions (Lewy bodies) in neurons 5

Atypical Parkinsonian Syndromes - Red Flags

These require specialist confirmation as they have different prognoses and treatment responses: 3

• Progressive Supranuclear Palsy (PSP): Vertical gaze palsy (especially downward), early falls, axial rigidity predominance 3, 4
• Multiple System Atrophy (MSA): Early severe autonomic dysfunction, cerebellar signs, pyramidal signs; alpha-synuclein accumulates in oligodendroglia rather than neurons 3, 5
• Corticobasal Degeneration (CBD): Asymmetric rigidity with alien hand phenomenon 3, 4
• Vascular Parkinsonism: History of stroke, hypertension, stepwise progression, lower body predominance 3, 4

Drug-Induced Parkinsonism

• Caused by dopamine-blocking agents (antipsychotics, antiemetics) 4
• Treat with anticholinergics or amantadine; consider discontinuing offending agent 4
• Must distinguish from negative symptoms in psychiatric disorders 4

Hyperkinetic Disorders

Chorea (Irregular, Flowing, Non-Stereotyped Movements)

Huntington Disease (HD) - Most common cause in adults:

• Autosomal dominant with CAG repeat expansion (>38 repeats diagnostic) on chromosome 4 1
• Onset age 35-45 years with progressive behavioral, motor, and cognitive symptoms 1
• Genetic testing is the diagnostic test of choice; imaging may be normal early 1
• MRI shows progressive caudate and putamen atrophy (disproportionate to cortical atrophy) 1
• CT is not preferred due to limited soft-tissue characterization 1

Systemic Lupus Erythematosus (SLE):

• Chorea associated with antiphospholipid antibodies/APS 1
• Most patients (55-65%) experience single episode lasting days to months 1
• Treat with dopamine antagonists; add glucocorticoids plus immunosuppressives (azathioprine, cyclophosphamide) for active NPSLE 1
• Antiplatelet/anticoagulation for antiphospholipid-positive patients 1

Other Chorea Causes to Exclude:

• Cerebrovascular disease, infections, autoimmune disorders, metabolic disturbances, drug-induced (levodopa, stimulants) 1

Paroxysmal Dyskinesias

Paroxysmal Kinesigenic Dyskinesia (PKD):

• Attacks triggered by sudden movement, last seconds to 5 minutes 1
• Patient remains fully conscious during attacks 1
• Distinguish from frontal lobe epilepsy: PKD has clear kinesigenic trigger, normal consciousness, occurs only when awake 1

Paroxysmal Non-Kinesigenic Dyskinesia (PNKD):

• Triggered by coffee, alcohol, stress, fatigue (not movement) 1
• Attacks last 10 minutes to 1 hour (longer than PKD) 1
• Lower attack frequency than PKD 1

Paroxysmal Exercise-Induced Dyskinesia (PED):

• Induced by prolonged exercise (5-30 minutes), not by coffee/alcohol 1
• Duration 5-45 minutes, typically under 2 hours 1

Rapidly Progressive Dementia with Movement Disorders

Creutzfeldt-Jakob Disease (CJD):

• MRI with DWI and T2-FLAIR sequences is optimal imaging 1
• T2 hyperintensity and diffusion restriction in cortex, basal ganglia (caudate/putamen 60%), thalami (13%) 1
• Pulvinar sign (posterior thalamus) or hockey stick sign (posteromedial thalamus) 1
• Hallmark: gray matter involvement with white matter sparing 1
• IV contrast helps identify alternative diagnoses (autoimmune, inflammatory) 1

Differential for RPD includes: 62% prion disease, 15% other neurodegenerative, 8% autoimmune, 4% infectious, with 17% potentially treatable 1

Dystonia

• Sustained muscle contractions causing twisting, repetitive movements or abnormal postures 2, 6
• Can be primary (genetic) or secondary (structural lesions, Wilson's disease, drugs) 2

Tremor

• Essential tremor: Bilateral action tremor, family history, improves with alcohol 6
• Distinguish from PD: Essential tremor lacks bradykinesia and rigidity 3

Tics

• Very brief jerks or dystonic postures, shorter than PKD attacks 1
• Tourette syndrome: Multiple motor and vocal tics 7

Myoclonus

• Sudden, brief, shock-like involuntary movements 2

Critical Metabolic/Genetic Disorders Not to Miss

Wilson's Disease:

• Consider in all patients under 40 with movement disorders, chronic hepatitis, or cirrhosis 1
• Kayser-Fleischer rings plus low ceruloplasmin (<0.1 g/L) establishes diagnosis 1
• 24-hour urinary copper >1.6 μmol/24h 1
• Movement disorders include tremor, dystonia, parkinsonism, chorea 1
• Requires lifelong chelation therapy 1

Neurodegeneration with Brain Iron Accumulation (NBIA):

• Consider in young patients with progressive dystonia and parkinsonism 1

Pediatric-Specific Considerations

• Sandifer syndrome: Head tilt after eating due to gastroesophageal reflux 1
• Benign paroxysmal torticollis: Recurrent painless head postures before 3 months of age, may evolve to migraine 1
• Transient dystonia of infancy: Onset 5-10 months, resolves by 3-5 years without sequelae 1
• Hyperekplexia: Excessive startle response to sudden stimuli, present from birth 1

Functional Movement Disorders

Red flags suggesting psychogenic etiology: 1

• Distractibility and variability between episodes
• Suggestibility
• Adult onset
• Altered responsiveness during attacks
• Medically unexplained somatic symptoms
• Atypical medication response

However, anxiety and depression are common in organic movement disorders (especially PKD), so psychiatric comorbidity does not exclude organic disease. 1

Diagnostic Algorithm

1. Establish phenomenology: Hypokinetic vs. hyperkinetic; identify dominant movement disorder 2
2. Obtain MRI brain without contrast to exclude structural, vascular, inflammatory causes 1, 3
3. For parkinsonian syndromes: Refer to neurologist for clinical diagnosis confirmation; consider I-123 ioflupane SPECT/CT if diagnosis unclear 3
4. For chorea in adults: Genetic testing for HD; check for SLE/antiphospholipid antibodies; exclude drugs, metabolic causes 1
5. For patients under 40 with any movement disorder: Check ceruloplasmin, 24-hour urinary copper, slit-lamp exam to exclude Wilson's disease 1, 8
6. For rapidly progressive dementia: MRI with DWI/FLAIR sequences; consider CSF 14-3-3 protein, EEG 1
7. For paroxysmal disorders: Detailed trigger history distinguishes PKD, PNKD, PED, and epilepsy 1

Common Pitfalls

• Failing to recognize atypical parkinsonian syndromes (PSP, MSA, CBD) that mimic PD but have worse prognosis and different treatment responses 3
• Missing Wilson's disease in young patients—always check ceruloplasmin and urinary copper 1, 8
• Ordering CT instead of MRI for initial structural imaging—CT has inadequate soft-tissue resolution 1, 3
• Assuming psychiatric diagnosis without excluding organic causes, especially in paroxysmal disorders 1
• Not obtaining specialist confirmation for parkinsonian syndromes—clinical diagnosis alone is challenging 3
• Overlooking drug-induced parkinsonism from antipsychotics, antiemetics, or other dopamine blockers 4