What are the Mathias criteria (autonomic dysfunction guidelines) for diagnosing and managing autonomic dysfunction?

Mathias Criteria for Autonomic Dysfunction

The "Mathias criteria" is not a formally recognized diagnostic framework in current medical literature or guidelines; however, the term likely refers to the systematic approach to diagnosing and managing autonomic dysfunction, particularly neurogenic orthostatic hypotension, which requires bedside orthostatic vital sign testing followed by comprehensive autonomic function testing when abnormal.

Diagnostic Approach to Autonomic Dysfunction

Initial Bedside Assessment

• Orthostatic vital sign testing is the primary screening tool, measuring blood pressure and heart rate supine and after 3 minutes of standing 1, 2
• Neurogenic orthostatic hypotension (nOH) is diagnosed when systolic blood pressure drops ≥20 mmHg OR diastolic drops ≥10 mmHg within 3 minutes of quiet standing 2, 3
• Postural Orthostatic Tachycardia Syndrome (POTS) is diagnosed when heart rate increases ≥30 bpm in adults (≥40 bpm in adolescents) within 10 minutes of upright posture WITHOUT orthostatic hypotension 2, 4, 3

Key Clinical Features Distinguishing Neurogenic from Non-Neurogenic Causes

Neurogenic orthostatic hypotension presents with distinctive symptoms that differ from simple dehydration or medication effects 1:

• Persistent and progressive generalized weakness and fatigue 1
• Visual blurring and cognitive slowing 1
• Leg buckling 1
• "Coat hanger" headache (triangular headache at base of neck due to trapezius ischemia) 1
• Symptoms provoked by exertion, prolonged standing, meals, or increased ambient temperature 1

Comprehensive Autonomic Function Testing

When bedside testing is abnormal or clinical suspicion remains high, proceed with formal autonomic testing 2:

Gold Standard Tests for Cardiovascular Autonomic Neuropathy

The most sensitive and specific approaches include 1:

1. Heart rate variability (HRV) - evaluates parasympathetic function 1
2. Baroreflex sensitivity (BRS) 1
3. Muscle sympathetic nerve activity (MSNA) 1
4. Plasma catecholamines 1
5. Heart sympathetic imaging 1

Specific Autonomic Reflex Tests

The Valsalva maneuver, deep breathing test, and orthostatic test (30:15 ratio) are gold standard methods for diagnosing cardiovascular autonomic neuropathy 3:

• These tests detect initial or subclinical abnormalities 3
• They assess severity and prognosis 3
• Tilt table testing should NOT be the first-line test for early-stage autonomic dysfunction, as it only detects advanced cases 3
• Tilt testing with a dysautonomic pattern (gradual blood pressure drop without heart rate increase) suggests cardiovascular autonomic neuropathy 3

When to Refer for Specialized Autonomic Evaluation

Referral for autonomic evaluation is reasonable (Class IIa recommendation) in patients with 1:

• Parkinsonism or other central nervous system features 1
• Peripheral neuropathies 1
• Underlying diseases associated with peripheral neuropathy 1
• Progressive autonomic dysfunction without central or peripheral nervous system features 1
• Postprandial hypotension 1
• Known or suspected neuropathic POTS 1

Excluding Secondary Causes

Screen for reversible and treatable causes before attributing symptoms to primary autonomic failure 2:

• Essential laboratory tests: HbA1c, fasting glucose, TSH, AM cortisol, ACTH, vitamin B12, B6, folate, thiamine 2
• Infectious screening: HIV, hepatitis B/C, Lyme disease 2
• Autoimmune markers: ANA, ESR, CRP, ANCA, anti-smooth muscle, SSA/SSB, RNP, anti-dsDNA 2
• Neurological markers: CPK, ganglioside antibodies, anti-MAG 2
• Serum protein electrophoresis 2

Medication Review

Medication-induced autonomic failure is a critical consideration 1:

• Tricyclic antidepressants 1
• Phenothiazines 1
• Antihistamines 1
• Levodopa 1
• MAO inhibitors 1
• Beta-blockers, calcium antagonists, ACE inhibitors 2
• Antipsychotics and narcotics 2

Distinguishing Primary from Secondary Autonomic Failure

Secondary autonomic failure indicates damage from other diseases 1:

• Diabetes mellitus (most common cause) 1, 3, 5
• Kidney or liver failure 1
• Alcohol abuse 1
• Among diabetic patients, 38-44% develop dysautonomia 3
• In diabetes, dysfunction progresses from parasympathetic involvement, then sympathetic, finally presenting as orthostatic hypotension 3

Primary autonomic failure includes 1:

• Multiple system atrophy 1
• Parkinson's disease 1
• Lewy Body dementia 1
• Pure autonomic failure 6

Neuroimaging Indications

MRI brain and/or spine is recommended when 2:

• Focal neurological signs are present 2
• Syncope occurs in supine position 2
• Cranial nerve involvement is suspected 2
• Concern for structural CNS pathology exists 2

Routine neuroimaging (CT/MRI) is NOT recommended in the absence of focal neurological findings or head injury 1

Common Pitfalls

• Do not use tilt table testing as the initial diagnostic test for early autonomic dysfunction, as it only identifies advanced cases 3
• Inadequate blood pressure monitoring when initiating treatment is a common error 2, 4
• Failing to recognize that supine hypertension develops in >50% of neurogenic orthostatic hypotension patients, creating therapeutic challenges 3
• Not distinguishing between neurogenic and non-neurogenic orthostatic hypotension, as the latter may be due to hypovolemia or medications and has different management 3