What could be the cause of an adult patient's symptoms of anterior sway while walking, xerostomia, and fatigue, considering potential underlying neurological or medical conditions and possible medication side effects?

Anterior Sway While Walking, Dry Mouth, and Fatigue: Differential Diagnosis and Workup

The combination of anterior sway while walking (gait instability), xerostomia, and fatigue most commonly results from medication side effects—particularly anticholinergic drugs, antihypertensives, or cardiovascular medications—or represents an underlying neurological, endocrine, or autoimmune condition requiring systematic evaluation. 1, 2

Immediate Medication Review

Medications are the most common cause of xerostomia and can simultaneously cause gait disturbance and fatigue through multiple mechanisms. 1, 2, 3

• Anticholinergic medications (antihistamines, antidepressants especially tricyclics, antimuscarinics, antiparkinsonians, antipsychotics) cause xerostomia, sedation, and CNS depression that impairs balance and causes fatigue 1, 2, 4
• Antihypertensive and cardiovascular medications produce dizziness, vertigo, and postural instability as side effects 1
• Diuretics, calcium channel blockers, lithium, and NSAIDs contribute to xerostomia and electrolyte disturbances affecting gait 1, 2
• Polypharmacy exponentially increases risk of these combined symptoms 1, 4

Neurological Causes Requiring Urgent Evaluation

Gait instability with anterior sway suggests cerebellar, vestibular, or basal ganglia dysfunction and demands neurological assessment. 1

Central Nervous System Pathology

• Posterior circulation stroke (brainstem or cerebellum) presents with gait ataxia, vertigo, and associated neurological deficits including fatigue 1
• Parkinson's disease or parkinsonism causes anterior-flexed posture, gait instability, fatigue, and xerostomia (from autonomic dysfunction or medications); adults with certain genetic conditions have 4-fold increased risk of early-onset Parkinson's 1
• Multiple sclerosis affecting brainstem/cerebellum causes ataxia, fatigue, and autonomic dysfunction 1
• Cerebellar disorders produce characteristic gait ataxia with anterior sway 1

Peripheral Vestibular Disorders

• Vestibular neuronitis causes acute vertigo, disequilibrium, nausea, and fatigue but typically does not cause isolated anterior sway 1
• Chronic vestibular dysfunction from various etiologies produces persistent disequilibrium 1

Endocrine and Metabolic Causes

Endocrine disorders commonly cause this symptom triad and are readily identifiable through laboratory testing. 1, 2, 5

• Diabetes mellitus causes xerostomia through autonomic neuropathy and osmotic diuresis, peripheral neuropathy affecting gait, and fatigue 1, 2, 5
• Thyroid dysfunction (both hyperthyroidism and profound hypothyroidism) causes xerostomia, muscle weakness affecting gait, and fatigue 1, 2, 5
• Hypocalcemia (from hypoparathyroidism) causes fatigue, muscle weakness, gait abnormalities, and can be asymptomatic or present with neurological symptoms 1
• Hypomagnesemia contributes to similar symptoms and often coexists with hypocalcemia 1

Autoimmune Conditions

Sjögren's syndrome and related autoimmune diseases present with xerostomia as a cardinal feature, often accompanied by systemic fatigue. 1, 2, 5

• Sjögren's syndrome causes the classic "sicca complex" of dry mouth and dry eyes, with profound fatigue as a major symptom; approximately 10% of patients with significant dry mouth have underlying Sjögren's 2, 5
• Scleroderma, rheumatoid arthritis, and systemic lupus erythematosus can present with xerostomia and systemic symptoms including fatigue 2
• Neurological manifestations of autoimmune disease can cause gait disturbance 1

Other Critical Considerations

Cardiovascular and Renal

• Congestive heart failure causes fatigue, peripheral edema, and postural instability; fluid retention can worsen at night 1
• Chronic kidney disease causes xerostomia, fatigue, and metabolic disturbances affecting gait 1, 2, 5
• Postural hypotension produces episodic dizziness and gait instability when moving from supine to upright 1

Sleep Disorders

• Obstructive sleep apnea causes nocturnal xerostomia (mouth breathing), daytime fatigue, and can be associated with gait disturbance from chronic sleep deprivation 1, 2
• Insomnia and restless legs syndrome contribute to fatigue and may worsen other symptoms 1

Systematic Workup Algorithm

Step 1: Comprehensive History

• Medication review: Document ALL medications including over-the-counter products, supplements, and recent changes 1, 2, 3
• Temporal pattern: Onset, duration, progression, and relationship to medication changes 1
• Associated symptoms: Numbness, weakness, tremor, speech disturbance, memory loss, autonomic symptoms (lightheadedness on standing, bowel/bladder dysfunction) 1
• Sleep assessment: Snoring, witnessed apneas, daytime somnolence, unrefreshing sleep 1
• Fluid intake patterns: Excessive thirst suggesting diabetes or compensatory drinking for dry mouth 1

Step 2: Targeted Physical Examination

• Neurological examination: Lower limb strength, deep tendon reflexes, gait analysis (observe for anterior flexion, ataxia, bradykinesia), speech assessment, tremor evaluation 1
• Oral examination: Assess salivation, look for scleroderma features 1
• Cardiovascular: Blood pressure (including orthostatic measurements), peripheral edema 1
• Fundoscopic examination: If skew deviation or central pathology suspected 1

Step 3: Baseline Laboratory Investigations

Order the following panel for ALL patients with this symptom complex: 1, 5

• Electrolytes and renal function (BUN, creatinine) to identify chronic kidney disease 1, 5
• HbA1c to screen for diabetes mellitus 1, 5
• Thyroid function (TSH) to identify thyroid dysfunction 1, 5
• Calcium and magnesium to identify parathyroid disorders 1, 5
• Urine dipstick with albumin:creatinine ratio to screen for renal disease 1, 5

Step 4: Autoimmune Screening (If Indicated)

Order autoimmune panel when: 2, 5

• Xerostomia is accompanied by dry eyes (sicca complex)
• Systemic symptoms present (joint pain, rash, Raynaud's phenomenon)
• No clear medication or metabolic cause identified

Panel includes: 5

• Anti-SSA/Ro antibody
• Rheumatoid factor
• Antinuclear antibody (ANA)
• Consider inflammatory markers (ESR, CRP)

Step 5: Neuroimaging (When Indicated)

Obtain brain MRI with and without contrast if: 1

• Focal neurological signs present (weakness, sensory loss, abnormal reflexes)
• Acute or subacute onset suggesting stroke or demyelination
• Progressive symptoms despite medication adjustment
• Ataxia with other brainstem/cerebellar signs
• Concern for central pathology (mass, stroke, multiple sclerosis)

CT imaging has very low yield (<1%) in patients with normal neurological examination 1

Step 6: Additional Testing Based on Clinical Suspicion

• Polysomnography if obstructive sleep apnea suspected (snoring, witnessed apneas, daytime somnolence, unrefreshing sleep) 1
• Lumbar spine MRI if bowel/bladder dysfunction or lower limb upper motor neuron signs present 1
• Electroencephalogram if seizures suspected 1
• Dopaminergic imaging if parkinsonism suspected and diagnostic uncertainty exists 1

Critical Pitfalls to Avoid

• Failing to review ALL medications including over-the-counter products is the most common missed diagnosis, as medications are the leading cause of xerostomia 1, 2, 3
• Overlooking sleep disorders as contributors to both nocturnal xerostomia and daytime fatigue 1, 2
• Dismissing xerostomia as trivial when it may signal serious autoimmune disease with 5% lifetime lymphoma risk (Sjögren's syndrome) 5
• Assuming peripheral vestibular cause without considering posterior circulation stroke, which can present without focal deficits in up to 75% of cases 1
• Missing hypocalcemia which can be asymptomatic or cause seizures, cardiac arrhythmias, and neurological symptoms 1
• Failing to measure orthostatic blood pressure when postural hypotension from medications or autonomic dysfunction may explain symptoms 1

Immediate Management Priorities

While awaiting workup results: 1, 6, 3, 7

1. Medication adjustment: Discontinue or reduce anticholinergic medications when possible; review antihypertensives for dose adjustment 1, 3
2. Symptomatic xerostomia treatment: Salivary stimulants (pilocarpine if residual gland function) are more effective than substitutes; ensure adequate hydration 6, 3, 7
3. Fall precautions: Given gait instability, implement safety measures 1
4. Urgent neurology referral if focal neurological signs, acute onset, or progressive symptoms 1
5. Rheumatology referral if autoimmune serologies positive or high clinical suspicion for Sjögren's syndrome 5