What are the steps for a neurological exam in a patient with suspected Ehlers-Danlos Syndrome (EDS), Mast Cell Activation Syndrome (MCAS), or Postural Orthostatic Tachycardia Syndrome (POTS) presenting with tongue numbness/tingling?

Neurological Examination in EDS/MCAS/POTS with Tongue Paresthesias

In a patient with suspected EDS, MCAS, or POTS presenting with tongue numbness/tingling, perform a focused neurological examination that prioritizes autonomic function testing, cranial nerve assessment for small fiber neuropathy, and joint hypermobility evaluation, as these conditions frequently involve peripheral and autonomic neuropathy.

Immediate Autonomic Assessment

Measure postural vital signs with active stand test as the first priority, documenting heart rate increase ≥30 bpm in adults (≥40 bpm in adolescents 12-19 years) within 10 minutes of standing without orthostatic hypotension, as this identifies POTS which affects up to 37.5% of hEDS patients 1, 2. Record baseline supine heart rate and blood pressure after 5 minutes of rest, then repeat measurements at 2,5, and 10 minutes of standing 3.

• Document any symptoms during position changes including lightheadedness, palpitations, visual changes, or worsening tongue paresthesias 4
• Note if systolic blood pressure increases on standing (from baseline to >10 mmHg elevation), which suggests hyperadrenergic POTS subtype commonly seen with mast cell activation 4

Cranial Nerve Examination Focused on Small Fiber Function

Assess cranial nerves V (trigeminal) and VII (facial) with particular attention to sensory distribution, as tongue paresthesias may indicate small fiber neuropathy or autonomic dysfunction affecting the lingual nerve 1.

• Test light touch sensation on all three divisions of trigeminal nerve bilaterally using cotton wisp, comparing affected tongue side to contralateral 2
• Evaluate corneal reflex bilaterally, as diminished response suggests small fiber involvement 2
• Assess taste on anterior two-thirds of tongue (CN VII) and posterior third (CN IX) using sweet/salty solutions 2
• Examine tongue for fasciculations, atrophy, or deviation on protrusion (CN XII) 2
• Check for soft palate elevation symmetry and gag reflex (CN IX, X) 2

Joint Hypermobility Assessment Using Beighton Score

Calculate the Beighton score systematically, as scores ≥5/9 in adults under 50 years, ≥4/9 for those over 50, or ≥6/9 for prepubertal children support hEDS diagnosis 1, 2.

• Passive dorsiflexion of each fifth finger >90 degrees (1 point per side) 2
• Passive apposition of each thumb to flexor surface of forearm (1 point per side) 2
• Hyperextension of each elbow >10 degrees (1 point per side) 2
• Hyperextension of each knee >10 degrees (1 point per side) 2
• Ability to place palms flat on floor when bending forward with knees extended (1 point) 2

Peripheral Sensory Examination

Test for length-dependent sensory loss pattern that may accompany autonomic neuropathy in these conditions 1.

• Assess pinprick sensation in stocking-glove distribution starting distally in feet and hands 2
• Evaluate vibration sense using 128 Hz tuning fork at great toes and fingers 2
• Test proprioception at distal interphalangeal joints of toes and fingers 2
• Document any allodynia or hyperalgesia, which may indicate mast cell-mediated neurogenic inflammation 5

Motor and Coordination Assessment

Examine for subtle motor weakness or coordination deficits that may result from chronic orthostatic intolerance or connective tissue laxity 1.

• Test strength in all major muscle groups using Medical Research Council scale (0-5) 2
• Assess for proximal muscle weakness, particularly in hip flexors and shoulder abductors 2
• Perform finger-to-nose and heel-to-shin testing for cerebellar function 2
• Evaluate rapid alternating movements (dysdiadochokinesia) 2

Reflex Examination

Document deep tendon reflexes systematically, as hyperreflexia may suggest central involvement while hyporeflexia indicates peripheral neuropathy 2.

• Test biceps, triceps, brachioradialis, patellar, and Achilles reflexes bilaterally using standard grading (0-4+) 2
• Check for pathological reflexes including Babinski, Hoffman, and jaw jerk 2
• Note any asymmetry that might suggest focal neurological lesion 2

Skin and Vascular Examination

Inspect skin for signs of mast cell activation or connective tissue disorder that correlate with neurological symptoms 1.

• Document presence of flushing, urticaria, or dermatographism suggesting MCAS 1, 5
• Assess skin hyperextensibility by gently pulling skin on volar forearm 1, 2
• Look for thin, translucent skin with visible veins (suggests vascular EDS) 2
• Note easy bruising patterns, atrophic scarring, or tissue fragility 2

Critical Pitfalls to Avoid

Do not attribute tongue paresthesias solely to anxiety or functional symptoms without completing autonomic testing, as 42% of POTS patients have laboratory evidence of mast cell activation that requires specific treatment 5.

• Avoid performing invasive diagnostic procedures if vascular EDS is suspected, as fatal complications have been reported 2
• Do not delay tryptase testing if patient presents with episodic multisystem symptoms (flushing, urticaria, wheezing, GI symptoms) beyond isolated tongue paresthesias 1, 3
• Recognize that beta-blockers should be used with great caution in hyperadrenergic POTS with mast cell activation, as treatment directed against mast cell mediators may be required instead 4

Additional Testing to Consider Based on Examination Findings

If postural vital signs confirm POTS, refer for tilt table testing and expanded autonomic function testing including sudomotor assessment 1, 6.

If examination reveals multisystem symptoms beyond tongue paresthesias (flushing, urticaria, GI symptoms), obtain baseline serum tryptase and repeat 1-4 hours following symptomatic flare, with diagnostic threshold of 20% increase above baseline plus 2 ng/mL for MCAS 1, 3.

If Beighton score is positive and patient has additional features (soft velvety skin, family history, systemic symptoms), apply the 2017 diagnostic criteria for hEDS available at https://www.ehlers-danlos.com/wp-content/uploads/2017/05/hEDS-Dx-Criteria-checklist-1.pdf 2.