AUTONOMIC DISORDERS
DISEASE SYNDROMES
1. Systemic diseases
- Diabetes Mellitus
- Amyloidosis
- Porphyria
- Infections
- Chronic renal or hepatic disease: Usually subclinical
2. Immune disorders
3. System Degenerations
- Idiopathic Orthostatic Hypotension
- Shy-Drager
Sporadic or Autosomal Dominant
- Clinical features
- Orthostatic hypotension
- Bladder & bowel incontinence
- Parkinsonism
- Ataxia
- Anhydrosis; Ptosis
- Onset: Adult
- Mitochondrial - MNGIE
(Myopathy and external ophthalmoplegia; Neuropathy; Gastro-Intestinal; Encephalopathy)
4. Hereditary
- Riley-Day (HSAN 3)
Chromosome 9q31; Recessive
- Clinical features
- Newborn: Hypothermia; Vomiting crises
- Reduced Lacrimal Flow
- Absent Fungiform Tongue Papillae
- Pain Insensitivity; Large fiber modalities relatively spared
- Absent deep tendon reflexes
- Older patients: Postural hypotension; Lack of taste
- Most patients Jewish
- Pathology: Marked reduction of unmyelinated axons
- Congenital sensory neuropathy with anhidrosis (HSAN 4)
Autosomal Recessive
Mutations in TRKA/ NGF receptor (Chromosome 1q21-q22)
Deletion, splice-site & missense mutations
In tyrosine kinase domain
- Clinical features
- Congenital insensitivity to pain
- Fever - idiopathic
- Episodic hyperpnea
- Mental retardation
- Self mutilation
- Laboratory
- No histamine axon flare response
- No tearing with mecholyl
- Absent small myelinated & unmyelinated axons
Ptosis & delayed eye-opening
Hypotension, hypoglycemia, and hypothermia
Progressive postural hypotension with exertion
Nasal stuffiness
Prolonged or retrograde ejaculation (normal erection)
Reduced exercise tolerance
Ptosis
- Laboratory
- Dopamine beta-hydroxylase deficiency
- Low plasma, urine, and CSF noradrenaline and adrenaline
- Increased plasma, urine, and CSF dopamine
- Treatment: L-dops - Elevates noradrenaline levels
Dermatographism
Excess sweating
Reduced body temperature
Intermittent sinus tachycardia
- Acoustic neuromas
- Obesity
5. Drugs & Toxins
- Polyneuropathy
- Cellular dysfunction: Pharmacologic
- Reduce sympathetic activity
- Sympathetic neuron: Guanethidine; Bethanidine
- a
-adrenoceptor blockade: Phenoxybenzamine; Prazosin
- b
-adrenoceptor blockade: Propranolol; Timolol
- Increase sympathetic activity
- Release noradrenaline: Tyramine
- Monoamine oxidase inhibitors
- b
-adrenoceptor stimulants: Isoprenaline
- Decrease parasympathetic activity
- Botulinum toxin
- Anticholinergic: Atropine; Probanthine
- Anti-arrhythmics: Disopyramide
- Increase parasympathetic activity
Carbachol; Bethanicol; Pilocarpine
Mushrooms: Muscimol & Muscarine
Reversible: Pyridostigmine; Neostigmine
Irreversible: Organophosphorus inhibitors
6. Primary Dysautonomia: Often monophasic + remission
- Acute
- Pandysautonomia
- Pure cholinergic dysfunction
- Dysautonomia but no postural hypotension
- Postural orthostatic tachycardia
- Gastrointestinal motility disorders
- Chronic autonomic failure
- Congenital: Nerve growth factor deficiency
7. Localized autonomic dysfunction
Autonomic Syndromes
- Gastrointestinal syndromes
Endothelin receptor type B ¡Error!Referencia de hipervínculo no válida.; Chromosome 13q22; Recessive ¡Error!Referencia de hipervínculo no válida.
- Short segment bowel disease in 95%
- Associated with deafness and pigmentary anomalies
Endothelin-3 ¡Error!Referencia de hipervínculo no válida.Chromosome 20q13.2-q13.3
Recessive or Dominant with reduced penetrance
- Congenital central hypoventilation with Hirschsprung disease ¡Error!Referencia de hipervínculo no válida.
- Autonomic sleep ventilation failure
- GI: Megacolon; Esophageal motility reduced
- Face: Antimongoloid eye slant; Triangular mouth
- Low-set ears; Small nose
- Heart rate control: Reduced
- Differential diagnosis
Depression of ventilatory response to hypoxia and hypercapnia ¡Error!Referencia de hipervínculo no válida.
Familial lethal sleep apnea ¡Error!Referencia de hipervínculo no válida.
- Chagas' disease (Trypanosomiasis cruzii)
- Gustatory sweating (Frey's syndrome)
- Familial visceral myopathy with external ophthalmoplegia ¡Error!Referencia de hipervínculo no válida.
- Eyes: Ptosis & ophthalmoplegia
- GI: Intestinal pseudoobstruction; Ascites
- Progression: Death often < 30 years
- Pathology:
- Loss of smooth muscle in stomach & intestines
- Peripheral neuropathy
- Post-surgical
- Regional sympathectomy
- Dumping syndrome: Post-vagotomy & gastric drainage
- Heart transplantation
- Heart rate
: Parasympathetic control
- Tachycardia
- Fixed: Diabetes mellitus; Amyloidosis
Cardiac parasympathetic failure
- Bradycardia
- Resting: Dopamine ß-hydroxylase deficiency
Parasympathetic sparing
Carotid sinus hypersensitivity
Swallow & vasovagal syncope
- Postural hypotension
(Blood pressure: Sympathetic, noradrenergic control)
- Causes
- Autonomic dysfunction:
- Low intravascular volume
- Vasodilation
- Reduced cardiac output
- Drugs: Amphetamines
- Exacerbation
- Rapid positional change
- Morning
- Large meals
- Prolonged recumbency
- Warm environment
- Increased intrathoracic pressure: cough; micturition; defecation; exertion
- Vasoactive drugs
- Treatment
- Avoid exacerbating factors
- Stockings
- Reduce salt loss: Mineralocorticoids
Fludrocortisone 0.1 mg qd to qid
Resistance vessels: Midodrine; Phenylephrine; Phenylpropanolamine 25 mg tid
Capacitance vessels: Dihydroergotamine
Indirect: Ephedrine; MAO inhibitors; Yohimbine
Prostaglandin synthetase inhibitors: Indomethacin; Flurbiprofen
Dopamine receptor blockade: Metoclopramide; Domperidone
b-2 adrenoceptor blockade: Propranolol
- Prevent postprandial hypotension
Avoid gastric filling: Smaller more frequent meals
Adenosine receptor blockade: Caffeine 250 mg
Strong coffee or tea before arising from bed & with meals
Peptide release inhibitors: Somatostatin analogue; Octreotide
Other medications: Ibuprofen 400 mg; Phenylpropanolamine 25 mg; Ergotamine Intranasal: 1 or 2 puffs
- Increase cardiac output: Pindolol; Xamoterol
- Increase red cell mass: Erythropoietin
- Reduce nocturnal polyuria: Desmopressin
- Avoid supine hypertension:
Reduce excessive fludrocortisone
No vasoconstrictors after 6 pm
Sleep with head of bed elevated
- Sweating
: Sympathetic; Muscarinic cholinergic control
- Hyperhidrosis
- Toxic: Arsenic; Hg (Inorganic); Acrylamide
- Riley-Day syndrome
- Compensatory for loss of sweating elsewhere
- May be initial symptom with progression to anhydrosis
- Gustatory sweating (Frey's syndrome)
Aberrant sympathetic, cholinergic axons supply facial sweat glands
- Unmyelinated, postganglionic, cholinergic axons in peripheral nerves
- Preganglionic sympathetic efferent axons
- Sweat glands
- Nocturia
- Postural hypotension
- Relocation of fluid from periphery
- Treatment: Desmopressin
- Bladder atony: Cholinergic dysautonomia
- Common in Shy-Drager: Lesion in sacral Onuf's nucleus
- Treatment
Scheduled voiding with double voiding techniques
Clean, intermittent self-catheterization
Infection prevention
- Sexual dysfunction
- Erection: Dependent on parasympathetic supply & Nitric oxide
Intracavernous injections of
Prostaglandin E, or Papaverine ± Phentolamine
Topical nitroglycerin paste
Physical: Surgery
- Ejaculation: Dependent on sympathetic system
- Ocular
- Horner's syndrome: Miosis; Mild ptosis; Facial vasodilation & reduced sweating
- Holmes-Adie syndrome
Autosomal dominant
- Dilated, myotonic pupil
- Areflexia
- Absence of lacrimation
- Sjögren's
- Congenital absence
Hair: Sparse
Teeth: Abnormal or missing
Anhidrosis: Due to lack of sweat glands
Hyperthermia: Life threatening or brain damage
Carrier females: Abnormal teeth
with deafness ; retardation ¡Error!Referencia de hipervínculo no válida.
- Riley-Day (HSAN 3)
- Congenital absence of salivary glands & lacrima punctata
Autosomal Dominant
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9/1/97
References
1. Neuropediatrics 1996;27:26-31
Taxol; Vacor; Vincristine 
; Chromosome 10q11.2; Dominant 