Autonomic Disorders
What Do You Need to Know?
- Neurogenic OH: HR increase <15 bpm on standing = inadequate baroreflex → think MSA, PAF, diabetic neuropathy, amyloidosis
- POTS: HR ↑≥30 bpm (or >120) within 10 min of standing WITHOUT hypotension; young women, often post-viral
- PAF vs MSA: both are α-synucleinopathies; PAF = peripheral only (low supine NE); MSA = central + peripheral (normal supine NE but fails to rise)
- AAG: anti-ganglionic AChR antibodies (α3 nicotinic) — the ONE validated autoimmune autonomic antibody; titer correlates with severity
- Valsalva Phase IV: absent BP overshoot = sympathetic adrenergic failure — most tested autonomic reflex
- Autonomic dysreflexia: SCI above T6 + noxious stimulus below lesion → hypertension + bradycardia — medical emergency
- Preganglionic neurotransmitter: ALL autonomic preganglionic fibers use ACh at nicotinic receptors (sympathetic AND parasympathetic)
Autonomic Nervous System — Quick Review
Sympathetic vs Parasympathetic
| Feature | Sympathetic | Parasympathetic |
|---|
| Origin | T1–L2 (intermediolateral cell column) | Cranial (III, VII, IX, X) + Sacral (S2–S4) |
| Preganglionic fiber | Short; ACh at nicotinic receptors | Long; ACh at nicotinic receptors |
| Postganglionic fiber | Long; norepinephrine (except sweat glands = ACh) | Short; acetylcholine (muscarinic receptors) |
| Ganglia | Paravertebral (sympathetic chain) + prevertebral (celiac, superior/inferior mesenteric) | Near or within target organ |
| Heart | ↑ HR, ↑ contractility (β1) | ↓ HR, ↓ conduction (muscarinic M2) |
| Pupils | Mydriasis (dilator pupillae, α1) | Miosis (sphincter pupillae, M3) |
| GI | ↓ Motility, sphincter contraction | ↑ Motility, sphincter relaxation |
| Bladder | Detrusor relaxation (β2/3), sphincter contraction (α1) | Detrusor contraction (M3), sphincter relaxation |
| Sweat glands | Eccrine: sympathetic cholinergic (ACh, muscarinic) | No innervation |
Key Anatomic Points
- Adrenal medulla: modified sympathetic ganglion — preganglionic fibers synapse directly; releases epinephrine (80%) + norepinephrine (20%)
- Sympathetic sweat glands: the ONE exception — sympathetic postganglionic fibers that release ACh (not NE)
- Horner syndrome pathway: 3-neuron arc — hypothalamus → C8–T2 ciliospinal center → superior cervical ganglion → eye
- Vagus nerve (CN X): provides ~75% of all parasympathetic innervation; heart, lungs, GI (to splenic flexure)
- ALL preganglionic fibers (sympathetic AND parasympathetic) use ACh at nicotinic receptors — this is why ganglionic AChR antibodies cause pandysautonomia
- Sympathetic postganglionic = NE everywhere EXCEPT sweat glands (ACh, muscarinic) — classic board question
Orthostatic Hypotension
Definition & Criteria
- Orthostatic hypotension: SBP drop ≥20 mmHg OR DBP drop ≥10 mmHg within 3 minutes of standing (or head-up tilt)
- Initial OH: transient drop within 15 seconds of standing (not sustained) — benign
- Delayed OH: BP drop after 3 minutes but within 10 minutes — may be early neurogenic OH
Neurogenic vs Non-Neurogenic OH
| Feature | Neurogenic OH | Non-Neurogenic OH |
|---|
| HR response to standing | <15 bpm increase (inadequate) | >15 bpm increase (appropriate) |
| ΔHR / ΔSBP ratio | <0.5 bpm/mmHg | >0.5 bpm/mmHg |
| Supine NE | Low (PAF) or fails to rise on standing (MSA) | Normal |
| Causes | MSA, PAF, PD, diabetic neuropathy, amyloidosis, AAG | Dehydration, hemorrhage, medications, adrenal insufficiency, sepsis |
| Supine hypertension | Common (loss of baroreflex modulation) | Uncommon |
| Valsalva Phase IV | Absent overshoot | Normal overshoot |
Common Medications Causing OH
- Antihypertensives (α-blockers, diuretics), dopaminergic agents (levodopa, dopamine agonists), TCAs, antipsychotics, nitrates, PDE5 inhibitors
Supine Hypertension
- Defined as SBP ≥140 and/or DBP ≥90 mmHg while supine
- Present in >50% of neurogenic OH patients — makes treatment challenging
- Management: elevate head of bed 30°, avoid supine position during day, short-acting nitro patch at bedtime (remove in AM)
Treatment of Orthostatic Hypotension
| Approach | Intervention | Mechanism / Notes |
|---|
| Non-pharmacologic | Compression stockings (waist-high) | Reduces venous pooling; abdominal binders more effective than stockings alone |
| Increased salt (6–10 g/day) + fluid (2–3 L/day) | Volume expansion; first step always |
| Counter-pressure maneuvers | Leg crossing, squatting, muscle tensing during symptoms |
| Head-up tilt sleeping (10–15°) | Reduces nocturnal supine hypertension + natriuresis; preserves morning volume |
| Pharmacologic | Midodrine | α1-agonist; peripheral vasoconstriction; avoid within 4 h of bedtime (supine HTN); do NOT give supine |
| Droxidopa (Northera) | Norepinephrine precursor; FDA-approved for neurogenic OH; converted to NE by DOPA decarboxylase |
| Fludrocortisone | Mineralocorticoid; volume expansion + ↑ vascular α-receptor sensitivity; watch K+, edema, supine HTN |
| Pyridostigmine | AChE inhibitor; enhances ganglionic transmission; modest effect; less supine hypertension |
- HR increase <15 bpm on standing = neurogenic OH (baroreflex failure) — the single most important bedside clue
- Droxidopa is the only FDA-approved NE precursor for neurogenic OH — know the drug name
- Midodrine is an α1-agonist — last dose ≥4 hours before bedtime to avoid supine hypertension
Postural Tachycardia Syndrome (POTS)
Diagnostic Criteria
- HR increase ≥30 bpm (or absolute HR >120 bpm) within 10 minutes of standing or head-up tilt
- In adolescents (12–19): HR increase ≥40 bpm
- WITHOUT orthostatic hypotension (SBP drop <20 mmHg)
- Symptoms present ≥6 months: lightheadedness, palpitations, tremor, exercise intolerance, brain fog
Demographics
- Female predominance (5:1), age 15–50
- Common triggers: post-viral (including post-COVID), post-surgical, post-concussion
Subtypes
| Subtype | Mechanism | Key Features |
|---|
| Neuropathic | Partial small fiber neuropathy → lower limb sympathetic denervation | Decreased sweating in legs (QSART abnormal distally); blood pooling in lower extremities |
| Hyperadrenergic | Excessive sympathetic drive | Standing NE >600 pg/mL; prominent palpitations, tremor, anxiety, hypertension; may have mast cell activation |
| Hypovolemic | Low circulating blood volume | Low plasma volume, low renin-aldosterone; inadequate volume for upright posture |
Associated Conditions
- Ehlers-Danlos syndrome / joint hypermobility — high comorbidity; connective tissue laxity → venous pooling
- Mast cell activation syndrome (MCAS), autoimmune disorders, small fiber neuropathy, chronic fatigue syndrome
Treatment
| Line | Intervention | Notes |
|---|
| Non-pharmacologic (first) | Fluid 2–3 L/day, salt 10–12 g/day | Volume expansion is cornerstone |
| Compression garments (waist-high) | Abdominal binder most effective |
| Graduated exercise program | Start recumbent (rowing, swimming); avoid upright exercise initially |
| Pharmacologic | Propranolol (10–20 mg) | Low-dose β-blocker; controls HR without worsening BP |
| Midodrine | α1-agonist; reduces venous pooling |
| Fludrocortisone | Volume expansion |
| Ivabradine | If-channel blocker; lowers HR without BP effect; emerging use |
| Pyridostigmine | AChE inhibitor; enhances ganglionic neurotransmission |
- POTS is NOT a diagnosis of exclusion — must meet specific HR criteria AND exclude orthostatic hypotension
- Standing NE >600 pg/mL = hyperadrenergic subtype — the one with the most dramatic palpitations and tremor
- Exercise reconditioning is the most effective long-term treatment — start recumbent, progress slowly
Pure Autonomic Failure (PAF)
Key Features
| Feature | Details |
|---|
| Pathology | α-synucleinopathy; Lewy bodies in autonomic ganglia (peripheral) |
| Presentation | Severe orthostatic hypotension, supine hypertension, anhidrosis, constipation, urinary retention, erectile dysfunction |
| CNS involvement | None — no parkinsonism, no cerebellar signs, no cognitive decline |
| Supine NE | Very low (<100 pg/mL) — confirms postganglionic failure |
| Standing NE | Fails to rise appropriately |
| MIBG cardiac scan | Reduced uptake (postganglionic cardiac sympathetic denervation) |
| Onset | Insidious, middle-aged to elderly |
Phenoconversion Risk
- 15–30% of PAF patients convert to MSA, PD, or DLB over years — longitudinal surveillance needed
- Predictors of conversion: RBD, cognitive changes, subtle motor signs, abnormal DaTscan
- If parkinsonism develops → reclassify as PD; if cerebellar signs → MSA-C; if early dementia → DLB
PAF vs MSA vs PD: Autonomic Comparison
| Feature | PAF | MSA | PD |
|---|
| OH severity | Severe | Severe (often >30 mmHg drop) | Mild–moderate (usually later) |
| Supine NE | Very low | Normal or mildly low | Normal or mildly low |
| Standing NE | Fails to rise (postganglionic) | Fails to rise (preganglionic) | Variable |
| MIBG cardiac scan | Abnormal (postganglionic) | Normal (preganglionic) | Abnormal (postganglionic) |
| CNS signs | None | Parkinsonism ± cerebellar | Parkinsonism |
| Lesion | Peripheral (postganglionic) | Central (preganglionic) | Both |
- PAF = peripheral α-synucleinopathy with isolated autonomic failure; if motor/cerebellar/cognitive signs appear → reclassify as MSA, PD, or DLB
- Very low supine NE = postganglionic lesion (PAF, diabetic neuropathy); normal supine NE that fails to rise = preganglionic lesion (MSA)
- MIBG scan: abnormal in PAF & PD (postganglionic denervation); normal in MSA (preganglionic lesion) — differentiates MSA from PAF/PD
Multiple System Atrophy — Autonomic Perspective
MSA Subtypes
| Subtype | Predominant Motor | Autonomic Failure |
|---|
| MSA-P (parkinsonian) | Akinetic-rigid parkinsonism; poor levodopa response | Severe; early and prominent |
| MSA-C (cerebellar) | Cerebellar ataxia, dysarthria, nystagmus | Severe; early and prominent |
Autonomic Features of MSA
- Orthostatic hypotension: severe (often >30 mmHg SBP drop); early in disease; with supine hypertension
- Urogenital: urinary retention/incontinence (early); erectile dysfunction often the earliest symptom in males
- Stridor: laryngeal abductor paralysis — nocturnal inspiratory stridor; can cause sudden death; may require tracheostomy or CPAP
- Cold, purple hands: vasomotor dysfunction; characteristic
MSA vs PD: Autonomic Comparison
| Feature | MSA | PD |
|---|
| OH severity | Severe, early | Mild–moderate, later in course |
| Urinary dysfunction | Early, prominent (retention + incontinence) | Later, milder (urgency/frequency) |
| Stridor | Present (≥30%); potentially fatal | Absent |
| Erectile dysfunction | Early, often first symptom | Present, usually later |
| Supine NE | Normal (preganglionic) | Normal or low (postganglionic component) |
| MIBG cardiac scan | Normal | Abnormal |
| Levodopa response | Poor or transient | Robust, sustained |
| Progression | Rapid (survival 6–10 yr) | Slow (survival >15 yr) |
Red Flags for MSA (vs PD)
- Early severe autonomic failure (≤5 yr of motor onset)
- Stridor (laryngeal abductor paralysis)
- Cold, purple hands
- Anterocollis (disproportionate neck flexion)
- Rapid progression; poor/transient levodopa response
- Early recurrent falls
Imaging
- Hot cross bun sign: cruciform hyperintensity in pons on T2 MRI — selective loss of pontine neurons/myelinated fibers (MSA-C)
- Putaminal slit sign: hyperintense lateral putaminal rim on T2 (MSA-P)
- Putaminal atrophy with hypointensity on T2 (iron deposition)
- Stridor in MSA = laryngeal abductor paralysis — can cause sudden death during sleep; may require tracheostomy
- Erectile dysfunction is often the earliest symptom of MSA in males — precedes motor by years
- MIBG scan normal in MSA (preganglionic) vs abnormal in PD/PAF (postganglionic) — key differentiator
Autoimmune Autonomic Ganglionopathy (AAG)
Overview
| Feature | Details |
|---|
| Antibody | Anti-ganglionic AChR (α3 subunit of nicotinic acetylcholine receptor) |
| Onset | Acute/subacute pandysautonomia over weeks to months |
| OH | Severe orthostatic hypotension |
| Sicca symptoms | Dry eyes, dry mouth (parasympathetic involvement) |
| GI | Severe gastroparesis, constipation, ileus |
| Urinary | Urinary retention (neurogenic bladder) |
| Pupils | Fixed, dilated (tonic pupils) — parasympathetic denervation |
| Sudomotor | Anhidrosis (global) |
| Motor/sensory | None — pure autonomic |
AAG vs Guillain-Barré Syndrome
| Feature | AAG | GBS |
|---|
| Motor weakness | Absent | Ascending paralysis |
| Sensory loss | Absent | Variable (paresthesias common) |
| Autonomic failure | Predominant (pandysautonomia) | Present but not primary |
| Antibody | Anti-ganglionic AChR | Anti-ganglioside (GM1, GQ1b, etc.) |
| CSF | Normal | Albuminocytologic dissociation |
| Analogy | “Autonomic GBS” | Motor/sensory predominant |
Paraneoplastic Association
- SCLC (small cell lung cancer), thymoma — always screen for malignancy
- Can overlap with other paraneoplastic antibodies
Diagnosis & Treatment
- Antibody titer correlates with disease severity — higher titer = more severe dysautonomia
- Autonomic testing: widespread sympathetic + parasympathetic failure on CASS
- Treatment: IVIg, plasma exchange (PLEX), rituximab, corticosteroids; treat underlying malignancy if paraneoplastic
- Some patients have chronic/relapsing course; may need maintenance immunotherapy
- Anti-ganglionic AChR Ab is the ONE validated autoimmune autonomic antibody — titer directly correlates with severity
- AAG = “autonomic GBS” — pure pandysautonomia without motor or sensory involvement
- Fixed dilated pupils + dry eyes/mouth + GI dysmotility + severe OH + urinary retention in an acute/subacute onset → think AAG
Autonomic Testing
Cardiovagal (Parasympathetic) Tests
| Test | What It Measures | Normal Response | Abnormal Indicates |
|---|
| Deep breathing (HR variability) | Cardiovagal function | HR varies ≥15 bpm with deep breathing at 6 breaths/min | ↓ HR variability = vagal neuropathy |
| Valsalva ratio | Cardiovagal + adrenergic | Longest RR interval (Phase IV) / shortest RR interval (Phase II) ≥1.21 | Low ratio = cardiovagal failure |
| Head-up tilt | Integrated baroreflex | Stable BP with appropriate HR increase | OH ± inadequate HR response |
Valsalva Maneuver — Four Phases
| Phase | BP | HR | Mechanism |
|---|
| Phase I | ↑ | Transient ↓ | Thoracic compression → aortic squeezing |
| Phase II early | ↓ | ↑ | ↓ Venous return → ↓ CO → baroreflex-mediated tachycardia |
| Phase II late | Recovery toward baseline | Sustained ↑ | Sympathetic vasoconstriction (if intact adrenergic function) |
| Phase III | Brief ↓ | — | Release of strain → transient ↓ BP |
| Phase IV | BP overshoot | Reflex bradycardia | Increased venous return into vasoconstricted bed → overshoot; baroreflex slows HR |
- Absent Phase II late recovery = sympathetic (adrenergic) failure
- Absent Phase IV overshoot = sympathetic (adrenergic) failure — the most tested Valsalva abnormality on boards
- Low Valsalva ratio (Phase IV bradycardia absent) = cardiovagal failure
Sudomotor (Sympathetic Cholinergic) Tests
| Test | What It Assesses | Key Points |
|---|
| QSART (quantitative sudomotor axon reflex test) | Postganglionic sympathetic sudomotor function | Acetylcholine iontophoresis stimulates axon reflex; measures sweat volume at 4 sites (forearm, proximal/distal leg, foot) |
| TST (thermoregulatory sweat test) | Pre + postganglionic (entire sympathetic pathway) | Indicator powder changes color with sweat; whole-body map; can localize central vs peripheral |
| Sympathetic skin response (SSR) | Sudomotor sympathetic pathway | EDA change to stimuli; highly variable; least reliable |
Localizing Sudomotor Lesions
- TST abnormal + QSART abnormal = postganglionic lesion (PAF, peripheral neuropathy)
- TST abnormal + QSART normal = preganglionic lesion (MSA, spinal cord)
Plasma Catecholamines
| Condition | Supine NE | Standing NE | Interpretation |
|---|
| Normal | 100–350 pg/mL | ↑ ≥2× supine | Intact sympathetic outflow |
| PAF | Very low (<100) | Fails to rise | Postganglionic neuron loss |
| MSA | Normal | Fails to rise adequately | Preganglionic (central) failure |
| POTS (hyperadrenergic) | Normal | >600 pg/mL (excessive rise) | Sympathetic overactivation |
CASS (Composite Autonomic Severity Score)
- Standardized scoring combining: sudomotor (0–3) + cardiovagal (0–3) + adrenergic (0–4) = total 0–10
- Used to quantify overall autonomic failure severity and track progression
- Absent Valsalva Phase IV overshoot = adrenergic (sympathetic) failure — highest-yield autonomic testing fact
- QSART = postganglionic; TST = entire pathway; TST abnormal + QSART normal = preganglionic lesion
- Supine NE low = postganglionic (PAF); supine NE normal but fails to rise = preganglionic (MSA)
Neurogenic Bladder & Sexual Dysfunction
Bladder Innervation
| Component | Innervation | Nerve | Spinal Level | Function |
|---|
| Detrusor muscle | Parasympathetic (M3) | Pelvic nerve | S2–S4 | Contraction → voiding |
| Internal sphincter | Sympathetic (α1) | Hypogastric nerve | T11–L2 | Contraction → storage |
| External sphincter | Somatic (nicotinic) | Pudendal nerve | S2–S4 (Onuf nucleus) | Voluntary contraction → continence |
UMN vs LMN Bladder
| Feature | UMN Bladder (Spastic) | LMN Bladder (Flaccid) |
|---|
| Lesion level | Above sacral cord (suprapontine or spinal cord) | Sacral cord (S2–S4), cauda equina, or peripheral nerves |
| Detrusor | Hyperactive (uninhibited contractions) | Areflexic (no contraction) |
| Capacity | Small (reduced) | Large (distended) |
| Sensation | May be preserved (urgency) | Absent |
| Voiding pattern | Urgency, frequency, urge incontinence | Overflow incontinence, straining |
| Post-void residual | Low (if no DSD) or high (if DSD present) | High (incomplete emptying) |
| DSD | Present if lesion between pons and sacral cord | Absent |
| Treatment | Antimuscarinics (oxybutynin, solifenacin), β3-agonist (mirabegron), botulinum toxin | CIC (clean intermittent catheterization) |
Detrusor-Sphincter Dyssynergia (DSD)
- Simultaneous detrusor contraction + external sphincter contraction (should relax)
- Occurs with spinal cord lesions between pons and sacral cord (pontine micturition center coordinates; suprapontine lesions have synergistic voiding)
- Results in high bladder pressures → risk of hydronephrosis, UTIs, renal damage
- Treatment: CIC + antimuscarinics; botulinum toxin to sphincter; alpha-blockers
Common Neurologic Causes
| Condition | Bladder Type | Key Features |
|---|
| MS | UMN (most common) | Urgency, frequency, urge incontinence; DSD common with spinal plaques |
| Spinal cord injury | UMN (above conus) or LMN (conus/cauda) | DSD if between pons and sacral cord; spinal shock initially → areflexia then spastic |
| Diabetic neuropathy | LMN | Insidious; decreased sensation → large-capacity, overflow incontinence |
| Cauda equina syndrome | LMN | Urinary retention (often early) + saddle anesthesia + bilateral leg weakness/pain |
| MSA | Mixed (central + peripheral) | Early urinary retention/incontinence — disproportionate to motor severity |
Sexual Dysfunction
- Erection: parasympathetic S2–S4 (pelvic nerve); Point & Shoot mnemonic — Parasympathetic = Point (erection), Sympathetic = Shoot (ejaculation)
- Ejaculation: sympathetic T11–L2 (hypogastric nerve)
- Erectile dysfunction may be the earliest autonomic symptom in diabetes and MSA
- Always consider medications (antihypertensives, SSRIs, antipsychotics) as cause
- DSD only occurs with lesions between pons and sacral cord — suprapontine lesions (stroke, PD) cause urgency but NOT DSD
- Cauda equina: urinary retention is a hallmark — LMN bladder + saddle anesthesia = surgical emergency
- “Point and Shoot”: Parasympathetic = erection; Sympathetic = ejaculation
Specific Autonomic Conditions — Quick Reference
Autonomic Dysreflexia
| Feature | Details |
|---|
| Who | Spinal cord injury at or above T6 |
| Trigger | Noxious stimulus below lesion (bladder distension #1, bowel impaction, skin pressure, UTI) |
| Mechanism | Uninhibited sympathetic discharge below lesion → massive vasoconstriction → hypertension; baroreflex-mediated vagal bradycardia above lesion (but descending inhibition blocked by cord lesion) |
| Symptoms above lesion | Headache (pounding), flushing, sweating |
| Symptoms below lesion | Pallor, piloerection, cool skin |
| Vitals | Hypertension (SBP can exceed 200) + reflex bradycardia |
| Emergency management | 1) Sit upright (lower BP); 2) Identify & remove noxious stimulus (catheterize bladder, disimpact bowel); 3) If persistent: nifedipine, nitropaste, hydralazine |
Autonomic dysreflexia is a medical emergency — SBP can exceed 200–300 mmHg, risking stroke, seizure, retinal hemorrhage, or death. Immediate identification and removal of the noxious stimulus is the priority.
Complex Regional Pain Syndrome (CRPS)
| Feature | CRPS Type I (RSD) | CRPS Type II (Causalgia) |
|---|
| Nerve injury | No identifiable nerve lesion | Defined peripheral nerve injury |
| Trigger | Fracture, surgery, immobilization | Nerve trauma (partial injury common) |
| Presentation | Burning pain, allodynia, hyperalgesia + vasomotor changes (temperature/color asymmetry) + sudomotor changes (edema, sweating) + trophic changes (skin, nail, hair) |
Budapest Criteria (Requires All 4)
- 1. Continuing pain disproportionate to inciting event
- 2. ≥1 symptom in 3 of 4 categories: sensory (hyperesthesia/allodynia), vasomotor (temperature/color asymmetry), sudomotor/edema (edema/sweating changes), motor/trophic (weakness/tremor/dystonia/trophic changes)
- 3. ≥1 sign at examination in ≥2 categories
- 4. No other diagnosis better explains the findings
CRPS Treatment
- Physical/occupational therapy (cornerstone), mirror therapy, graded motor imagery
- Pharmacologic: gabapentin/pregabalin, TCAs, corticosteroids (early, short course), bisphosphonates
- Interventional: sympathetic nerve blocks, spinal cord stimulation, intrathecal baclofen (for dystonia)
Baroreflex Failure
| Feature | Details |
|---|
| Cause | Damage to baroreceptors or NTS (nucleus tractus solitarius) — post-neck surgery, radiation, bilateral carotid body tumors |
| Presentation | Labile hypertension with tachycardia (volatile surges); may alternate with hypotension |
| Key distinction | Hypertensive crises with tachycardia (unlike pheochromocytoma: also episodic but catecholamines elevated) |
| Treatment | Clonidine (central α2-agonist to reduce sympathetic outflow); benzodiazepines for acute crisis |
Hyperhidrosis
| Type | Distribution | Key Features |
|---|
| Primary focal | Axillary, palmar, plantar, craniofacial | Onset in adolescence; bilateral, symmetric; worse with stress; family history common |
| Secondary generalized | Generalized/diffuse | Think: autonomic neuropathy, lymphoma, pheochromocytoma, carcinoid, hyperthyroidism, menopause, medications |
Familial Dysautonomia (Riley-Day Syndrome)
| Feature | Details |
|---|
| Gene | IKBKAP/ELP1 (elongator complex protein 1) |
| Inheritance | Autosomal recessive |
| Population | Ashkenazi Jewish (carrier frequency ~1:30) |
| Pathology | Loss of sensory and autonomic neurons (small fiber > large fiber) |
| Classic findings | Absent fungiform papillae (smooth tongue), absence of tears (alacrima), orthostatic hypotension without compensatory tachycardia, pain/temperature insensitivity, episodic vomiting/hypertensive crises |
| Diagnosis | Genetic testing; absent axon flare with intradermal histamine injection |
| Prognosis | Median survival ~40 years; recurrent aspiration pneumonia is major morbidity |
Horner Syndrome
- Triad: miosis + ptosis + anhidrosis (ipsilateral)
- 3-neuron sympathetic pathway: 1st order (hypothalamus → C8–T2), 2nd order (ciliospinal center → superior cervical ganglion), 3rd order (SCG → eye)
- Cocaine test (blocks NE reuptake): fails to dilate Horner pupil (confirms Horner)
- Hydroxyamphetamine test: dilates = preganglionic (1st/2nd order); fails to dilate = postganglionic (3rd order)
- Cross-referenced in neuro-ophthalmology
- Autonomic dysreflexia: SCI ≥T6 + noxious stimulus below lesion → hypertension + bradycardia; bladder distension is the #1 trigger — catheterize first
- Riley-Day: Ashkenazi Jewish + absent fungiform papillae + alacrima + orthostatic hypotension = IKBKAP/ELP1 mutation
- Baroreflex failure: post-neck surgery/radiation + volatile hypertensive surges with tachycardia — treat with clonidine
- CRPS Type I (no nerve injury) vs Type II (identifiable nerve injury) — same clinical phenotype, different etiology
References
- Freeman R, Wieling W, Axelrod FB, et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res. 2011;21(2):69-72.
- Gibbons CH, Schmidt P, Biaggioni I, et al. The recommendations of a consensus panel for the screening, diagnosis, and treatment of neurogenic orthostatic hypotension and associated supine hypertension. J Neurol. 2017;264(8):1567-1582.
- Vernino S, Hopkins S, Wang Z. Autonomic ganglia, acetylcholine receptor antibodies, and autoimmune ganglionopathy. Auton Neurosci. 2009;146(1-2):3-7.
- Vernino S, Low PA, Fealey RD, et al. Autoantibodies to ganglionic acetylcholine receptors in autoimmune autonomic neuropathies. N Engl J Med. 2000;343(12):847-855.
- Benarroch EE. The autonomic nervous system: basic anatomy and physiology. Continuum (Minneap Minn). 2020;26(1):13-30.
- Fanciulli A, Wenning GK. Multiple-system atrophy. N Engl J Med. 2015;372(3):249-263.
- Kaufmann H, Norcliffe-Kaufmann L, Palma JA. Baroreflex dysfunction. N Engl J Med. 2020;382(2):163-178.
- Chelimsky TC, et al. Autonomic testing. In: Clinical Autonomic Disorders. 3rd ed. Lippincott Williams & Wilkins; 2008.
- Sheldon RS, Grubb BP, Olshansky B, et al. 2015 Heart Rhythm Society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome. Heart Rhythm. 2015;12(6):e41-e63.
- Harden RN, Bruehl S, Perez RS, et al. Validation of proposed diagnostic criteria (the “Budapest Criteria”) for complex regional pain syndrome. Pain. 2010;150(2):268-274.
