What are the possible diagnoses for an 84-year-old female with a mouth resting tremor progressing to difficulty with walking and transferring due to lack of coordination and strength?

Differential Diagnosis for 84-Year-Old Female with Mouth Resting Tremor and Progressive Gait Dysfunction

The most likely diagnosis is Parkinson's disease (PD), given the resting tremor and progressive motor dysfunction in a patient within the typical age range (peak onset 60-70 years), though atypical parkinsonian syndromes—particularly progressive supranuclear palsy (PSP)—must be strongly considered given the prominent gait and transfer difficulties. 1

Primary Diagnostic Considerations

Parkinson's Disease (Most Common)

• Classic presentation includes resting tremor, bradykinesia, and rigidity, with symptoms appearing after approximately 40-50% of dopaminergic neurons in the substantia nigra have been lost 1, 2
• The mouth/facial tremor is consistent with PD, which characteristically presents with resting tremor that can affect various body parts 1, 3
• At 84 years old, this patient falls within the extended age range for PD onset, though slightly older than the peak (60-70 years) 1
• Critical caveat: PD typically responds well to levodopa therapy, so lack of response should prompt reconsideration of the diagnosis 4, 3

Progressive Supranuclear Palsy (Most Common Atypical Parkinsonism)

• PSP is the most common atypical parkinsonism with prevalence around 5/100,000 and classically presents in the sixth or seventh decade (mean age 63) 1
• Patients characteristically present with lurching gait and axial dystonia manifested as unexplained falls—this matches your patient's difficulty with walking and transferring 1
• Early prominent gait dysfunction and postural instability are red flags distinguishing PSP from typical PD 1
• Vertical supranuclear gaze palsy is the classic finding but usually appears later in disease course 1

Multiple System Atrophy (MSA)

• Typical onset is 55-65 years with mean disease duration of almost 6 years 1
• MSA-P subtype (striatonigral degeneration) presents with predominant extrapyramidal/parkinsonian features 1
• MSA-C subtype presents with ataxia and cerebellar symptoms predominating, which could explain coordination difficulties 1
• Look for autonomic dysfunction (urinary incontinence, orthostatic hypotension) as distinguishing features 1

Vascular Parkinsonism

• Must be considered given advanced age and potential vascular risk factors 1
• CT or MRI can identify underlying vascular disease or structural lesions 1
• Typically presents with lower body predominant symptoms and stepwise progression 1

Less Common but Important Considerations

Corticobasal Degeneration (CBD)

• Typical onset 50-70 years with asymmetric limb clumsiness progressing to unilateral limb rigidity and dystonia 1
• Less likely given the mouth tremor presentation, but consider if asymmetric limb involvement develops 1
• Look for cortical features: apraxia, cortical dementia, cortical sensory deficits, impaired language production 1

Wilson's Disease

• Although rare in this age group, Wilson's disease can present with tremor (including characteristic "wing-beating" tremor), dystonia, and parkinsonian features 1, 5
• Neurological presentation can include akinetic-rigid syndrome similar to Parkinson's disease, pseudosclerosis dominated by tremor, ataxia, or dystonic syndrome 1
• Drooling and oropharyngeal dystonia are characteristic manifestations—relevant to mouth involvement 1
• Check serum ceruloplasmin and 24-hour urinary copper; look for Kayser-Fleischer rings on slit-lamp examination 1

Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS)

• Clinical features usually begin in the 60s with action or intention tremor followed by cerebellar ataxia, though 20% have only ataxia 6, 5
• Approximately 40% of male and 16% of female premutation carriers develop FXTAS 6
• Consider if family history of fragile X mutation or if patient has parkinsonian symptoms with neuropathy and psychiatric problems 6, 5

Neuronal Intranuclear Inclusion Disease (NIID)

• Rare neurodegenerative disease that can present with resting tremor enhanced by cognitive activity and walking 7
• Diagnosis made by skin biopsy findings 7
• Should be considered when tremor similar to PD is present but levodopa and anticholinergics are ineffective 7

Drug-Induced Parkinsonism

• Review medication list for dopamine-blocking agents (antipsychotics, antiemetics like metoclopramide, calcium channel blockers) 8
• Typically bilateral and symmetric, with less prominent resting tremor than idiopathic PD 8

Diagnostic Algorithm

Initial Clinical Assessment

1. Characterize the tremor precisely: resting vs. action, frequency, body distribution, factors that worsen/improve it 1, 3
2. Assess for cardinal parkinsonian features: bradykinesia (slowness of movement), rigidity (cogwheel or lead-pipe), postural instability 1, 2
3. Evaluate gait pattern: shuffling, festination, freezing, wide-based ataxic gait, or lurching gait with falls 1
4. Check for red flags suggesting atypical parkinsonism: 1
   • Early prominent falls (PSP)
   • Rapid progression
   • Poor or absent levodopa response
   • Early autonomic dysfunction (MSA)
   • Vertical gaze palsy (PSP)
   • Asymmetric cortical signs (CBD)

Essential Investigations

1. MRI brain without contrast is the optimal imaging modality to evaluate parkinsonian syndromes 1, 2

   • Identifies patterns of regional volume loss characteristic of MSA, CBD, or PSP 1
   • Excludes structural lesions, vascular disease, or hydrocephalus 1
   • May be normal in early PD 2

2. Laboratory workup for secondary causes: 1

   • Serum ceruloplasmin and 24-hour urinary copper (Wilson's disease)
   • Thyroid function tests (hypothyroidism can cause bradykinesia)
   • Serum ferritin if restless legs symptoms present
   • Consider FMR1 DNA testing if family history or clinical suspicion for FXTAS

3. Therapeutic trial of levodopa/carbidopa: 4, 3

   • Robust response supports PD diagnosis
   • Poor response suggests atypical parkinsonism or alternative diagnosis
   • Start with carbidopa-levodopa to reduce peripheral side effects 4

Critical Clinical Pearls

• The combination of mouth resting tremor with prominent early gait and transfer difficulties is atypical for classic PD and should raise suspicion for PSP or MSA 1
• Correctly diagnosing a parkinsonian syndrome on clinical features alone can be quite challenging, and imaging remains an essential diagnostic tool 1
• At 84 years old, consider that multiple pathologies may coexist (e.g., vascular changes plus neurodegenerative disease) 1
• Document response to levodopa therapy carefully—this is one of the most important diagnostic and prognostic indicators 4, 3
• If tremor is refractory to first-line medications (levodopa, dopamine agonists, anticholinergics), consider second-line agents (clozapine, amantadine, clonazepam) before concluding treatment failure 3